Choroidal

naevus
Choroidalnaevi are prcsentin 5-10%of Caucasiansbut
arevery rarein dark-skirmedraces.Theycanbeassociated
with NF1 and the dysplasticnaevussyndrome.Although
they are probablypreient at birth, growth occursrnainiy
during the prc-pubertal years and is extremelyrare in
adulthood.For this reasonclinjcallydetectable
growLh
snouroarousesusPrclon
oI ma[8nanc],

Histo!ogy
Thetumoul is composedoI a Plolileration of spindlecell
melanoc)'tes(Fit. 12.21A).

S,gns
1.
_ Prsntatifi.Thevastrnajorityof naeviareasymptomatic and detectedby routineexamination.
Rarely
s).mptoms
maybecaused
byinvolvemmtof ihfovea
by thetumowitrelf or by serousrctinaldetachment.
2. Signeof a tlaical naevui
. Usuallypogt-equatodal,
oval or circular,brown
to slate-greylesionwith hdistinct martins (Fig.
12.218).
. Dimensions
are<5mmin basaldiamte(i.e.3disc
diameters)
and<1rnmthickneso.
. Surface
drusmfilay bepresent,particularlyin the
cmtralareaof a largerlesionfFig.12.21C).
. Secondary choroiid neovaicularizatronrs
. Typicalnaevidonotrequle follow-upbecause
the
rbk of malignanttransformation
i6extremelylow.

lnvestigations
l. Photogaphy as a baselinerecord is good practice.
2, FA findings depmd on the amouit;f pismentation
within $e nie\,us and associatedchange;fr the overlyinS RPE.Most nievi are avascdar td pigmented,
dving rise to h)pofluorescencecausedby bl6ctrageof
backgound choroidai fluorescence.U rhe lesio; ;s
associatedwith surfacedrusnand RPEdetachment,
thb wiu tesult in areas oI ht?erfluorescence(Fit.
12.21DJ.
fA is not helpftrtin d;stinguish;ga smail
melaromafrom a naerls a-lrhough;dtiple-pinpoini
arasol h)?e uorescncemuy pieai.t tui*.gt6"rtr.
3. ICCA showshypofluorescmce
relativeto the surrouidins choroid (Fig. 12.21E).
4. Ulhasonogaphy tUS)showsalocalizednat or slightly
elevatedlesionwith hith internal acousticreflecivi{'
(Fig.12.21F).

Atypical
naevus

. Documentedgrowth.
. s].rnproms
su(h ,s blurred vision.meraftorphop.
sra/nerdtossand photoDsja.
.
.5 mm in diameter d1d >r
mrr h
P,ll:jl:*
Tracesof surfaceorantepigment0jpofuscin).
Aosence
or su acectrusenon a thicklesion.
Margrnof thelesionat or nearth opticdisc

*1.,r d."rg.tr:"r eflheroverrheswfaLe

T1:!r,
of the lesionor inJeriody.

these.fearues,
thehisher
P"^f^"jj:ijry.lTE
th chanceihat the lesion"f
is a melanoma.
MarLaffmenl invoheE basellnefundu3 phorograDh!
ano urnasonogaphy,
anctften indefinjLe
fol;wi,f,
lf growth has been docummted, the lesion
be reclassified as a melanoma aird
accordin8ly.

Dlffercntial
diagnosis
1, Congenitalhyperirophyo{ th RpEis darkand
with a well definedourline.
2. Melanoct'tomn of the choroid is clinicalh I
guishableftom a larte naelars.
3. Smrll melanomais associated
with serous
detachmmt and clumps of orangepigment.

Chorcldal
melanoma
Choroidalmelanoma
hasanovemllincidence
of 5-7
million?eryearin westemhemisphere
countdes
signficant genderdifference.It js the most (

primary inhaocular maljgnancy in adults and

Ior 80%of all uveal melanomas'.

Pathology
1. CeI ttTE
a. Spmdlecells are aranged in tight bundles;
cell membra-nes
areindistincr anAthe cl'roDlt

thillary or finelygranular.Nuclel'vaiy
slmderto pludrpandnucleolimayor may
distinct [Fig. U.AA).
b, Epithelioid cells arelargr and morc pleotr
thanspindleceUs,often;ppeafinq polihedr
abundant eosinophilc cyiopt*.. ni" c"tl
banes are distinct and an eihacellular space
separatesadjacentcells.The nuclei are larye
a coarsechromatinDaftemand Drominnt
oli. Mitotic figues are more ftequent ttEri,

spindlecells(Fig.12.238).
2, Clae6iffcation
of uvealmelanomas.
a, Spindle.ell melanomasfomredexclusively

spindle cells.
b. Mited cev fielarcIJ.asin which thereis a
of spindle ard epithelioid ce s.
3. Ofher histological featus
L Fascicularpaften of cell Fowth which may
Susplcrous
naeyus
vasocentic in whjch the cells are arrar$d t
1, Clinicalfatu.res.
The foUowintsuy sugSestthdt a
pendicularto a cmtsdl vess'fi8. l2.23(t
me anoc)fi. testonisnot.naenrsbutasnrallmelanonra.
dbbon-1ile
. An amelanotic
naevus(Fis.12.22,4).
. A'halo'naevu( which isiurollnded bv a pale
zone
resemblingchorcidatatrophy (Fig. 12.ZiB).'

...., ,.,.,1,.,,...
'
"l-",. ,- :: r

.r''

tig122r
chororda
naevus.
pfoliie*tion
shows
oi meafocttes
ir ihechoroid
{a)r-tisroogy
butsparngthe
chorocapi[ar]sl
(C)naeluswithsurfacedrLrsen;
lBlt}p.a naevus:
ofthe naevLrs
{D)FAshowshypofluorescnce
andhyperfluofescence
of
0r1lsen,
retarrle
ro thesunound
ngchofoid;{RB-scan
ltl /CGAshowshypoUloresrence
showss ightetevatorwithh gh
nernaacoustic
tfectvilv
Laun*t ott Hany- nE.A, M jlantczaktlNtcta tie f)

b. N?c/oslswherthc celltype rnaynot be rcognizable(!'is.12.23D).

a. Fanernof iumours'preaal
is asfollowsi
. Pentration
of Bruchm..nbane andihe RIE with
hemiation into the subrethal space,often with
the developmentof a 'collarsrud' shap (fig.
12.238).

lnvasionof sclralcharmels
for btoodvessets
and
neNesreslrlhngin orbiiatsprad(rig 12.23F).
hvasronot vortexveins.
Ve.a5l,n.l"er.roSenou.spr";oro Le li\er drd
occasronatlv
to thelungs bone,sl in and brain.
Oo.. rerve n a-:on,. rery ..re b. I n,\ oc.ur'1
eyeswith larte peripapittary
melanomai.

49i

498
5. Location.Anterior tumoursinvolving ciliary
bodt,
have a. vrors prognosis, mosi ljkety ,
are retarvety more advanced by the time

;1

dHer.onservdrivF
I pdnnpnr
l::y*(e
" l":1llT.l-y
rs as\oLraled
wrih oao, ru1.\J. t t. is prcUatfi
beca!setherecurencis an indrcationtharl

"' .""
",i;;;;;;. ;;;;;;ylis.i,ii,til "^n

Slgns
1. Presentationpeksat around the age of 60 yea$
turd
occursin oneof the foilowing waysi
.
mour.usud y U. rhe periph1r isymptomahc
ery.
r. dele.tcdby Lfdn.eon roLtinfund-sexam.
ination prformedfor otherleasons.
. A symptomatictumour causes
decreasedvisral
a.uih blunin8.melamorphopsra.
vjsua.fieldlos,
rrodte|C
or phoroPsiJ.
^.
rrSns
. Arolitary levared,subietinal,domc_shaped
mase.
hhj(,hmavb. prSmcnted
rFig.t2.7aAro;tess;-

'"""r'";"i"""f;.
ii ; i;:t*;;'il;ffi:;":;
usualiygreyor browni

. About60""of rumours
arelocdted
wjthh I mmat
the
u'e uPu(
optic orsc
disc or rovea,
fovea.

ai;6;-";;;s;;;.*t

,.er,"qu",,try

,een
n i,
jhe_RPF
o\erlyi;8ihciumour
{rig.r2.24b).
li ine tumourbredk\tlu-ougrBruchmenbrane
it
dLquiresd'.olldr-srud' appFdra.lcF.wjrh visible

blood vsselrrf lh tum;ur is amctanotic

'

flg,12,22
Unusual
choroidai
naevi.lAlpresumed
ametanotic
'halo'naevus
naevus;
lB)
- tlEA)
otBDanaro
lcounesy

Adv
eBe Wognosti
c factors
1. Histolodral featurs impl) in8 an adve-e prognorrs
r.lcludeldr8enumber"of epithetioidcells.tong and
wide "uclcr mDltiplenucldji. clo,edvasculartoop.
wiihin the tumour and lyrnphocyticinitifahon.
2, Claomosomal abnormalities within the mlanoma
cells,particularly loss of cluomosome3 and gans rn
.ru,ollosome
8,ire asocratedwirn a poororogno.-.
cains in the short arm of chromosbme6 caFy a
favourablprognosis.
3, Siz. Large tumourc have a worse prcmosis than
small tumours becauseof lead tima bi;s (i.. the
tumourandany metdiasesbeingpresentfora lonte.
njTF) dnd because
Lhe)reld to cho!\ dSCrec.ive
his_
tologjcaland rytogenetjcfeahu.es.
4. f\trabclerale\tension becdxqethc tumouri. rro"e
likely io be advancedand aggessive.

12.24D\.

A drrru5etumour i5 rare dnd is Lhdracteri,,ed

an rxtensiv flat or slightiy nised morph

wun grey o! brovrn iregular discoloraiion
12.248).
Exudativeretinal detachment,initia y conjined
the su{acc of ihe rumour and whicL law shi
jnJeriorlyand bcomes
bulous fIis. 12.24I).
Unlrle rhetmatogenous
rtinal d;hchment,
subretinal fluid shifts wiih ocular movmnt
gravity (shifiing fluid,). In addition, the
doesnot showthe fine, silvery rippting that
m tne presmceot a tear.
O$er sigis rncludeLhorojddtfotds,inbao.uldr
mllamnalior. haerqorrhate.
ruoeoiF rrjdir. secondaruglaucoma
and caiJaLt.

Specla/
inyestrgations
Aithough binocular indirect ophth?imos.opy
ltiih indjrecl .lirJdnD biomiiroscopyjs :ulficienrror
diagnosisin thevasimajorityof caseiitretotlowingnay,:
be useful
L FA is of limited diagnosticvalue bcaustherejs no
Pathotnomonic pattem. The most commonfindings .
are intrinsic tumour (dual') circdation (fjg. 12.25A)
aid laLF ddtuse lFakage'and ctainir-q. rA rnay,
h o w p \ p r be
h p 'us.ful
R p r , , l,rn
. iihe
A - differerriJ
r r g - - - a r ;"d;agro.i.
i.-".ic
ol
of
howerer.

sirutarusesion,
iuih ai,i","bii
and hamonhagiciesions.

"r""!"e'"*'

i,r,:r ff!

c.

:':l

F r
.\

(t,'
fig12l! lllsrologvof chorcdat me anoma 0) spindc cc ts rghuv atrangedfus iorm ce s wilh nrjistirctcc
nernbranes
a n ds c n d e ro r p r r m po v a /f u c e r ;( r ) c p l h ei o d c c r s i a r g cp t e o n o r p h cr ce s w i l hd s t n c l c e m e r n b r d r ersa r 8 e
vesrcLrar
f r u c e i w i tphr o m i n e nnlu c o l ,a n da b L r n d acnyrr o p t a s m
l Ct )i a s c c ! a r p a t t e r f- v a s o c e n r f i(cDi )n e c r oot r u n r o u , c e r y p e
c a n n obi e d e t e r mf d i { E )p n e t r a t t oont E r u c hm e r n b r a nr e
n i j c o t a r . s r u di a s h o n j( F ) e r l r a o caur e x t c n s o na f d a n
efnbollsof neopastc ce ls wlfin a b ood vesse
l h r 4 e s :a t t H a r !

tesAat;dEt)ua'yahttcitiscr,trr\ctucltDptlhdtii.ktholn!!tslne atltturenat,aa1

nlscDLardF)

2 USls usfulin dricciingtumoursrlhen ih. rncdiaar 3 , ICGA usuallyshowshyponuorescenc.

rtrouthoxi
Ofa.luean.1io shorrerh.aocular
exicnsionlt rs atso
the stldv and provides-norelnformaiionthan IA
uslIul in masuringtumourdimenslons.
Thecharacaboutth exintof ih tumolr, becalsihereis lcss
ter'lsiicfindjngsare intemalhonrgnefty,choroidal
mteriercnc
causedb,vRpEchanges.
" crot: 1 and orbr..t. "do" -t t-r; :.2"8 .
M R - r . r . h \ o e - i r. n . : t , t { . c i j 1 . F o- " g e - , tr o
o d - tud o Llgu'..ror :. , - o- p"l-. d oro L
r l 2 ( D \ " o h \ o o r , ,a t 2 - , F g F t F o r r d t ,b- ;
(Iig.t2 2sC).
theseleaiLrres
arenot pafiopromoftc.Enhancement

c-horoidalrnelanoma.
F|g12.24
pigfiented
{A)Hrghty
metaroma;
melanoma;{c)
o6nge
rneranoma
0) arneianolc
withsurface
pigmenl;
(D)'co arstud rnelanorna
wilhintrinsrc
vesses;(q diffusmanoma;
withsubtotatretinal
O argem;tanoma
GDUn5yat B Danata fgs A, CandFtrADSia1h,ltahci;ni5t Apmhal']l rhthaL4j Etseriet,2AA7fiE.E)

501

fl! r2r5 rmaging

in choroidar
melanoma.
0) FAearryphaseof a 'co ar,st,d'tumourshowsa ,duarcircubrron,;
of
{8)B,scan
a domeshaped
tumourshowschoroidalexcavation;
(C)B-scan
of a ,co ar_stud,tumour;
Tl weighned
0)
MR
shows
a
choroidal
rnelaroma
(whitearrow)andextraocular
extension
lblackarrow)

(cfunestaf B Danata- flgsA andB:s Muenki- fi| ct M

tatatcmk^ul$

tig.D)

with gadoliruum
improves
irnaSe
guatiry.demonsh.at_
r,'rgopLicrerve and orbitalinvdsionand facilirarinS
diflrentiationfuomothei tumours.
2.
Colour<odedDoppler inaging may diiJ,entiate
tsom haemorrhaSe.
PrSJrenlpd.turnourq
pdrrj.utarly
$ eyeswith opaqumedia.
S Biopsy is usefulirhen the aliamosiscannorbe establishedby lessinvasivemethod-s.It may b pedormed
e rherwith . 6neneedlor usingrhe25-grreevieeclo'ry .y.tem,lhe larrerprovidhg d targer,a;pte.

Slstemic
lnyesiigations
i

brea\trn women.Ocrasionajly,
Lheprimarysjtei! the
Kldneyor gastromtestmaltsact.
Delecti.ngposbibje ll)eh6tatic spread frcm the
cnorcroDecause
ot tartetujnoursjre(e.s.basajdiam_
eier > 16 mm) and if theris ctinicajsuipicion of meta_
staticspread.Hepaiicinvolvementcanbe aletectedby
ut!'a.o.1ography,and
etevated,aclale
deh\drutenase,
fraisDeprjdase
dnd dt(d,inephos_
tdo'lmd-gtuLrmyl.
p}latacelevets.Chctradiography
raretyshowqlun6
seLonoalesf the abselceof li\er rnetasLase.
o t
,bourl-2%of patient.ha\edetecrable
meta-rdrer
dr
the hmeot presmtation.

Systmic
investigationis ajmedat the Iollow.ng:

Ptinciples
oftreatnent

1. Excluding a metastasisto the choioial, most

frequently fiom ihe lung in boih sexesand ftom th

Treatnerr i. perlormed to avoid LLedeveloDD"enioI a

painjd and isjgtrly eye o,efe-abtycon+ninga. much

usefulvision as possible.Sinceit ls noi known when

metastasis
occursit is uncedainas to wherheror not
ocularfeatmani influencessurvlval.Theoreiically
thc
-mrllcrrhelunou, rhegredt,,,heopto,tuninrorprevenlrnS
nreli.to.ndrd $(.eIoreI'reaoh urSenr
is r-F
nedtoriieatment.
Management
shouldbeiailoredto the
hdividual. patient iaking th followjng factors inro
'

Size,locationand extentof the tumou togetherwith

etiectson visi.n
. Stateof th fellow eye.
' Gnralhealthand ageof the patient.
. Thepatient'swishesandfearc.
'lierimenl
(a-p.
mdyrol be -pqurrcd
in rnetollowing
. lf th tumour is slow-groydngand presntin the onty
seeingcyeof a very lderlyor chronicallyiI patient.
. If it is not possibleto detrmineclinicallywhethera
tunour is a smalimelanoma
or a latgenaevus.In this
casetha lesionis observed
and treaimentis adminislercd onl\ if Srowlh i, docunrented
by .cqu(nndr
u hasonog'aphy
or photography.

BrachJ4hercpy
B'd.\yrhcrdpvrrpisLle'alplrquc rrdiothFrapy)
wirtrurhenruml06
or dr iodinF-t)5
rDpti.ato,
rtrC.l2.264J
is usuallythe ircaimntof first ctiolcctecarlsdrt:srera,
lively straighlfonoard
andeffectiv.
1. Indicationsare tumoursless rhan 20 rnm in basal
diameterin whichthreis a rasonable
chanceofsal
vagingvision.]t is possiblero tfeat tumoursup to
5 mm'rlcl wrthd rutherumptaquc
dndup to t0 nm
lhicI.wirh aniodincpldqu.. :u pplenenral iran"pup:tlary lhcrmolherapv
rra) h rquired to srFrilirerhe
tumouror to reduceexudation.
2. Technique
a. the tumour js localized by transillumination or
binocularindirect ophthalmoscopy.
b. A tmplate consisting of a d$parent plastic
dumny or metalling with eyelersis suturedto the
sclerawith a releasablebow
c. Oncit has ben estabiishdrhat the remplateis
conectly positioned,the sutufesare loosenedand
useclto secur.theradioactive
plaque.
d. The plaque is removed onie tie appropriate
dose has ben deiivered,usually within 3*7
days.At least80Gy shouldbe deljveredro rhe
tumou apex.Tumour regressionstartsabout 1-2
months alter tlatment and continuesfor seveml Fig.12.26
Brach',therapy
for choroidat
rnetanoma.
6l
years, leaving a nat or dome-shapedpigmented P acement
of plaque;18)arnelanotic
tumourpriofto
rotowing
treallrenr0) p,cTenGrron
veatmelr
3. Tumour rcsponseis usually gradual.Amelanotic
tumours tend to becomemore pigmented
as they
regess(Fig.12.268and C).
4, Complicalions
dependon rn.i7eof therumouJa]^o
macularoedema,retinal hard exudates,serousrcdnal
rts obtan.e ro-1 optic ne^e dnd fovea.ploblem.
detachment, rubeosis and neovascular glaucoma
hom excessiveiradiation include caiaract,papillopa_
('toxic tumour s],Idrome').
ihy (with or wiihoui disc neovasculalzatidn) jnd
5, Survival. is similar io thal followinS enucleationfor
maculopathy.The inadiaied iumour can also cause
compalaDE
tumolus.

-;
Etr 'ij.i i;.-:.t!' i'!iiii:t::ii.1,,:
iradrdrjonh jth (hargdparti.le"suchasprotonsacrueve.
a hiE\ dosein lhe tumourwirh a relafiv;lysmaUdosein
thsu/ericial iissues.
1. Indications aretumofts unsuitablefor hachythelapy
eithet becauseof large size or posterior location
making positioning of a plaqueunrliable.
2. Te.hnique
a. Radio-opaquetantaium marke$ are sutwed to
the sclera and used to locate the tumour
radiographically.
b. The patimt is seated in a mechanized chair
with the head immobilized.
the patient dirccts gazeat a! adjustablefixation
larget.
d. Fourfractions
ofradiotherapy
aredeliveredover4
consecutivedays,

c. Adjunctive plaqueradiothenpy is administered,if

posebte,ro prevenLrecunencefrom deepintrd_
d. The treatment is repeated if ther is tesidual
iumour alter six months.
Tumour responseis giadral, with the lesion fust
becomintdarke-r
andllaHer,evenrualty
djsappearing
Complicationsincluderetinaltlactior! rctinal tearformationwjth rhegrnatogmous
deLachment,
vascular
ocLlusion,npovascuiariation
and iris b ms, which
canbe associated
with lensopacities.Localrecurmce
is cornmo& especiallyif the tumour is thick, amelanotic or involving the disc mattin.

Tftns-scleraI choroidectomy

Choroidectomyis a dilficult procedue and is the&fore

Tumourregr$Bionisslowerthanwith tradtytherapy not perfolmed widely. It may be indicatedlor catefuIy
,.aid choloiAalahophyaroundtle baseof th6tumour selectedtumouJsthat that are too thick for radiotherapi
but usually lessthan 15 mm in djamter.Complicatii;
iakeslongIto deiel;p.
Complicationsinvolving inhaocularstructutesale include retinai detach$mt, ocujar hypotony, wound
similarto tracht'thenpy.Extraocular
comDlications dehscenceand locai tumour recurrenci.

indudelossof tlshes,;ie[d depigmentati6rr

canaticulitiswith epipholaconjunctival
keratinization
and Enucleation
keratitis.
aresimilarto thosefollowingbrachy- 1, Indications for e\c.isronol the globeare larye tumour
Suryivalr3ult6.

Eize,optic disc inva6io&extensiveinvolverimt of the

ciliary body or angle,ifleversiblelossof usefil.lvision,
and poor motivation to keepthe eye.
tacticndiothercpy
2, Te.hnique is the 6ameas lor oiher condjtions,u6int
the surgeon'sprcfefied orbital implant. It is essentiai
on is focu6edon the turhourby almingmuttiple,
to perfdrm-ophthallrloscopyarqerdraping the patient
collirnated
bearnsfromdifJereitdire*ions,eith.'
to ensurethat the conect eyfu tleated,
or sequentially,so thai odly the tumour
a high do3eoI ndiation. This is still a new tech- 3, Complicatione are the sameas with enucleationfor
other onditions.Orbital recurence i6 rare if there is
whichb gainingin popularityin cenheswhere
no exbaoculartumour spreador if any suche\teruion
beafilradiotherapyis not avaiiable.Tle indicais completely
ercbed.
contraindicationsand complicationboI the6etwo

arelikely to besi[tilar'.

ry themothenpy

Differcntial
dia$nosis
Thefollowing conditioru shouldbe consideredin ihe dil-

thermotherapy(I'fI) usesan infrared ferential diagnosisof atypicalcasesl

to inductumoUIcelldeaihby hyperthemia
notcoagulation.
It is ausefrrladjmctto radiotherapy. 1. Pigm ed lsiont
Indicationr
. SmaI, pigmentd c Uoidal tumour whm dilfetentiation between naerus and melanomais not
possible and when radiotherapy is considercd
'

Small choroidal mlanomawhen radjorherapyis

inapprop ate becauseoI poor generathealth or
reducedlife expectancy.
' AJter ndiotherapy, as a treatmentfor exudation

tfueatening
vision,
2 Technique
a. Overlapphg one-minute applicationsof a 3mm
diode laserbeam ate applied all over the tumour
$]Iace, adjustingthe power soihat retjnal blanch_ mg doesnot devlopbelore45 seconds.
b. A 2mm m of smourdint choroid is treatdto
PrcVenrmargmalrEcurrenc,

. Large naevus usually shows numerous surlace

dnse& without srous retinal detachrEn ano
little if any onnge pigmmt.
. Velanocytoma b depty pjtmented and usually
locatedat ureoPbcdisc.
. Congenitalh'?errophy oI the RpEis tat and hns
a well-definedm.rgin.
. Haemorrlage in the subretinal spaceor suprachoroidalspaceasftom choroidalneovascujari?ation or rctirul artery macroaneurysm,
. Metastatic cutaneousmelanom; has a smooth
surface,a ljght brown cotour, indjsrinct margins,
exlensive retinal dehchment and often a past
history of maligmncy.
2. Non-pigmentedlesions
. Cfucumscribedchoroidat haemangiomajs q.?ically posterior, pink, dome+hapid, and has a
smoomsurnce.

li

Meiastasisis often associatedwith exudative

retinal detachment.
Solirary(noroidalgranulorr,aq
aqsocia
leo$ ilh sarcoidosisor tuberculosis.
Posteior scledtis,which can presmt with a large
elevatedlesion,but in contast ro melanomapam
rs a commonteature.
Large elvated discifo n lesio& which can be
eccentricallylocated,usualy in the temporalPleequatorialregion, and are usually associaiedwith
hard exudatesand hesh haemonhaAes,both of
which rarely accompanya melanomai
Prominent vortex vein ampulla is charactedzed
by a small, smooth, browr! dome-shaped
iesro4wrucnorsaPpear-s
on e\erlrnt pressureon

lit,, i:r,'eili
The followinSJray be Lsedro lleat \ ision_drreateniip
iumours.
I. Photodyrumi(themp) lpD-T)urinSthesamcmehod
as ror chorolddtneovasculdriTatjon.
Tle treahnmt
na)-needro be repated
a,,lerd tew n-onttuifsubr;inal ituio persjsts.
2. tTf Ior lesionsnoLin\otvingrhema(uta,lhough
tl[is
causeFperiphenl visual field loss.
3. R.diotherapymay
in! oivelen*sparing
exrernal
bean
p'"!"", bearrl radioLherapy
or
ptaque
Ir,:,,1:"",
bachytherap],

..
onl) a low dose
neeoeo,but even tht5 Lan .ause collateral
"r,"6;"rr,"ripi"ii
damageio

normal ttssus.

4, Intraviheal anti-VEGF thenpy showspromse.

;
"ii

diagtosis
Circumsgiled
ch0r0idal
haemangiomaDifterential
!. Arnelanoticchoroidalmelanomahas a yellow_tan
A circumscribedchoroidal haenangiomais not associLorout,ottm with subtleintnnsicdarkerpigment. .
^
ated-with systemicdisease.It may te dormant ihrouglF
2,
Choroidrl merastasis
is usually .riai
out life or may gjveriseto sympt6ms.
ard maybemdtifocal.Hota'eu"r,
usuallyasa resuu
,iLetustuti"
ot. cxudalive retjnal derachment.Slighr proFessive
from.carcinoidrumour, rmal cell carcrnomaang
enargementcan occurover many years,
rnyrold carcmomamay appear orarge, similar to a

namangrona,

RIE detachment
is acoustically
hollou ard shows
dEtmclpaitemon FA.
Posteriorscieitis is associated
with painandhas
lerent ultrasonographic
features,includmg sc

Dlagnosis
1, Histology showsa masswithin the choroidcomposed
of varyinS-sized
vascutar
(Fig.t2.27Ai
channets
2. Pre8entationis in the 2nd-4th decade!in one of the
followmg ways:
. Unilateral biutint of central visioir, visual field
defector metamorphopsia.
. Hypermehopiamiy occul iI the retina is elevafed
by tumou! or fluid.
. Asymptornatic with normal visual acuity, ar an
ircidental findinS.
3, Signs
. An oval orange massat the posterior Dole with
indistinct martiru thaLblendwrth the surrounding
choroid (Fig.12.278).
. Subretinallluid is usually presentin symptomatic

thi&eningandepiscleral
oedema.

Diffuse
choroid
al haemangioma
Diffusechoroidalhaemanqjoma
usuallvaJfects
over
of Lherhorojd and enJargeivery s)owly. Ir occursaJ:

exclusively
in patientsl,;ith ih-Sturs;Weber
ipsilateralto thenae\,usflammeus{s'eeCh.1).

1. Presentation
is usuallyin the2nd decadedespihtl
fart that the turnour ii presentat birih.

2. Signs

. The median basediameter of the lesion $ o mm

and the median thicLness3 mm.
. Complicationsindude surface6houj metaplasia,
cvsloid retinal degererdtjon,RpE deqeneration
and subretinalfi brosis_
{. FA revealsr.pid, spottvhvperfluore<cence
in thepreanerialor eariyarti;al phaseCig. I2.27C)anddifiu.e
rntenslatehl?erfl uorescmce.
5. ICGA showsiyperlluorescence
in the earty names
(Frt. 12.27D)
and hypofluorescence
I washo;l) aL20 5,
8. US shows an acoustjcallysolid lesion with a sharp
antedor sudace/ without choroidal excavationand
orbiialshadowmstFiq.1227E!
7. MR bhowsrhaljfie i;our i6 isG or hvDerinrense
ro
the vibeousin l-reighted imaeesan; isointmsein
T2-$itnredunages wiit^ m,a.ftd enl"ncerent b)
gadolinium.

. Thefundushasa diffusedeep-rcd,tomato
lek
coiourthat js mosrmarkedat ihe posterior

(Fig.12.284).

. Locali4d areasof rh;ckminq,simujatinqa cirl

scibed haemangioma,
may be prerent"Orhin
cliifuselesion.
US showsdiffusechorojdalthickeninafFis.12
Complicatio$ include secondary ieiinb r
degenerationaad eudative retinal detacbment.
vascuiar glaucoma can result i{ exudative
dtachment
is not Feated.

Treatmentol vision-tfueaienine
casesinvolveslowdoseradiotherapy
or PDT. "

9pllicdilgmelanocytoma
Me'arocytouu(maFlocelluJar
naewsJis a rare,disture
tive.unildteral.
heaviiypigme-redconqeniLal
hdmafloma
whichn seenmostfrequentjtin rheoo:ticnervehead
bul
which canrarelyanseanlwherein theuvea.In

l,'4,'

$
t..

t|g,12,27
CircLrmscf
bedchorotda
haemansorna.
{
sted congested
vascuarchanresforminga
masswirhtn
m.ss
rh..h.f.irr
^,""_
,^
\r(hrn
thecho,ord,
n(a apoearance:
tB)r
lctlpt^01:Fy-s"lols-varytng
FA,earVprrase
"
""""."""".
sr,olGiyperlroi;:;il'ffi&siil5:;;i,
"r,
nvpe
rfuorescence
i {E B-sc!n showsan a. ousi..itv sotjdtdston
wi6
a
sta
ri
anrerioi
.;;"
_
;;;;;
"
o mernaretectvity
o ( ,{1 r o r ll n o o i d ae \ c a r a t o n d , d o r o t a l s r " d o ; n g
{Rs,daceibtoJsrelaprasa

lcotrtestati tkty

tig.A)p citi tiCsEjC anttD; A Danda- fiEsE andr)

505

4, FA shows densepercistent hypofluorescencein aI

phasesof the angioSramdueto blockag(Fig.12.29D)
5. Complications, which are rare, ;nclude maligna
transforrnation,sPontaneoustumour necrosis/optic
and retinalveinobstru.tion
nerveLomp'e"sion
6. Treatmentis noi requiredxceptin lh very rare evmt
of rnaliSnanthansformation.

osteoma
Choroidal
Choroidalosteomais a very rare beniSn,slow-growin&
ossi$ins tumour which hasa very strongfemalepleponderarce.Bo& eyesare alfectedin about 25%of casesbur
not usually simultaneously.

Diagnosis
1. Histolo$/ shows mature cancellous bone, which
causesoverlying RPEatsoPhy.
Presentationis jn the 2nd-3rd decadswith gadual
visual impairment iI the macula is involved by
ihe tumour itself or by secondary choroidal
neovasculari tion.
Signg
. A yellos white llat or minimallvelevatedlesion
wiih well-define4 scallopedmargrnsnearthe disr
or at the postelior pole (Fit. 12.30A).
. Slow growth may occur over severalyears ar'd
longtanding casesmay develop RPE danges
(Fig.12.308).
' Spontaneousresorption and decalcificationnay
, rarely occur.
. Promosisis poor iJ $e lesioninvolvebthe fovea.
FA ma;ifestba;lv, irrsular, diftuse mottled hvpe!
(Irg. 1230qj chorcidal
fluores.ence
andlite sta-ining

(l) Diffusechoroidal
haemangioma;
tl!,12.2E
l4 sscan
thickening
showsdiffusechoroidal
- l1E.
B)
olBDznato
rcounesy
to choroidal melanoma,melanoq4omasare relatively
more commonin dark-skimed hdividuals and have a
fematepredominaica.In mostcasesthe tumour is station_
ary with little tendencyto change.

neovasculazationmaybeevidmt.
and
(Fig-12.30D)
IccA showsearlyhyp;fluorescence
late stainint. The tumour appearslarger that on
oDhihalmoscopv.
-higt'ly
rellectiveanteriorsurfaceanrl 'i
6, ut showsa
,l
orbitalshadowing
ig. 12.30E).
i
tha
at
th6
opaciry
oPaciE
dinse plaquelile
7, CT demonshates';
demonstrates'id;nse
olaouelil<e
leveloI thechoroid(Fig.12.30I).

dia9nosis
Differcntial

1. Choroidal mefastasis,which may alsobebilateral,but

typicauyafeclqan olderageSroup
2. Amelanoticchoroidal naevusot melanomadoesnot
causesucheriensiveorbitalshadowing.
polyhdral
deeplyPiSmented
1. Histologyshows,la'8e,
O66eou3metaplasi4 which may occur h assocralon
3.
or spindlecellswith qmallnuclei(fi8. 1229 ./
with chorojdalhremangionl,..
and lhe
2, Presintation.Mo"l casesaie asymptomatic
{. Sclerochoroidalcalcfication is an uncommonconor
condiiion is detected on routine ophthalnoscopy
yellowtionc\ardcLerledbv multilocalgeoqraphi.ai
(meanage50 years).
white fundus lesionl which areu-'udlit fould 'n boih
3, SiSns
eyesof older adults (seeFi& 8.21A).
' A dark brown or black ftat or sliShtly elevated
lesion with feathery edgesthat may extend over
rh. cdr, ^f rl" ,1i". aFid l, taB)

. Occasionallya larSetumour occupiesmost of the

discsurfaceand ma) Ieadto pi8menidi.pers'on
into the vifeous (Fi6.12.29C).
. An aJferentpupillary conduction defect may be
presmt, evenif visual acuity is tood.

tumours
Metastatic

Th choroid is by lar the most common site for uveal

metastases
acco;tins for about90%,followd by the iis
and ciliary body. Thi most ftequent pdmary sjte is tn
breastand brorichus.A choroid'alsec6ndary"maybe ihe

| ), ,1.,;5 0 7

rtl?29 Meldno.vtom? (aJh,!toog! shows heavly pigmente.l potyhedrdt

ce ts; 18)retativey flat lumoLrri rarge etevated
lc)
l , r o . : P ) r A - l o i , I \ p o r J o , a , p n .F o ' r J e " p e d
, , . L \ , () \ p j . d J . t o b o . . d p e
(tarrtestnt B Danalo tia A; p GIti ti! E)

initialprcsentauon
of a bronchjatcarcinoma,
whcrcas
a p"si hisiory oI brcastcanceris thc rule in patients
w j l l rb ? 5 r - . . , n d . , r ( - L. r t h F.r, . - , o n m o np r i m r r y
sitsincludethe gasrrointestjnat
tract,kidncl an{i skin
mlanoma.
Thc prosrahis, howevcr,an exiren1ety
rar
primarysitc.Patienisurvivatis genaraltypoor, wm a
mdianof 8,12,nonths.

12.31C)
althoughtheynevererhibita,musnroom
coff'gurahon.
. T i Fd ' D o \ i - , n r t r i f , r a t
(fig.,2.1.D,rnrbuur
-0'
"
o' prLiFnl.
dndb.th .r e, i." ;",.,u",, ,.,,

. Secondaryexudativ. retjnai
detachmentrs ire_
LruFnl
"rd^Tdyo rur Fy". w,thrFtdtivety.f,.l
deposih(Fjg r2.3181.
3 US may be usefui]n detectinga deposit,particularty
Diagrosis
rr evesw - :ef.ndd) e\udd;.ereruldl
oetd.-.'lenL.
L Presentationis usually with visual imDairment
A o r r ' , o i d " touur, + o h . d r J t u , r ,oL,tu r d r t . n i . . e l i 1 8
altloughmeiastass
na)' be asymptonaticij rocatcd
|| 18 |l. (l n A don -h"pcdlp5roashoh- rod, ;
"
a,,ravhom themacuta
rLervtutn mtp-nd^ounjc .eflecri\i$rjToughoJr
"p turou. htL h .. -ugge-.,v.bJ. nor o,lhoSro_
. ,^ lasi-gro&'ing
creamy,whjte
placojdtesiunwm
moni.
ndjstrnctmarginsmosttiequ;nrlytocaieoar rne 4. FA showsearly hypofluorescence
and diftuselai
porteriorpole (Iit. 1231A)rhatnav occasiona
y
r t o l nr.t b L l i - L o r r / - , r l ' , h o , o i d d l m e d r o m d . .
b l a . tp r g r F r ,, . - m p .o r r i . u r . - e , r r !
".hjbiL
oualcfcutatlon is fot seen
t2.1lBl
5. ICGA usuallyshowshypotluorescence
ttuoughihe
. n.or, -a-e-.\e dFpo.:..
,rF g,obuiar,, -.
siudy
and
may
show
subite
depos;rs
not
e\4oenron
"p,
-Ft"nord ,lrt
FA
"n ,net"nor.

rlr

Fig.12.30
Choroldal
(A)Earyjunapapjtary
osteoma.
lesjon;{B}ong-standing
tumourwithoverlying
RpEchanges;
{C)FAlate
phaseshowsmotted hyperfluorescence;
(|)lICGA
eartyphaseshowshypoiuorescence;
{q Bscrnshowsa hlghyrcnedive
antrlor
sudaceandorbitashadowing;
(RaxatcTdmonstrates
blatefatestons
as bone
thathaveihe sameconsisiencv
P ail

frasc adttD)

n9.12.31
Choroidal
(AlSmattplacoddeposit;
ptgment
metastasis.
clumpsonthe sudaceof a largedepositi
{B)secondary
q largedomeshaped
(01muttipte
deposit;
deposts;{g depostts
abovethe discandin thetemporalfLrndus
withshaltow
nlero' .etinaloetachnent;
o. a ptacoio
tesion
fi) B-scan
lcolnesJ/
ot c Brrry tE a anllE; B Danato fi| B)

510
6. Biopsy by fine needleaspilaiion or usinS a 25-gaug
vltledomy system may be appropriar when rhe
pnmary sneN untnown.

Sy,slefiic hyestgaijojrs
S\srenlCinve-srigrtio.1!
thepriman
dreainreddl iocarinS
tumour.rl uJl].nowndndodrermeldstati(
.rlF..Tht mdy
include ihe foilowinS:
.
'
.
.
.
'
.

FUI history ard physicalxamination.

Manmography ir fernales.
Chesiradiographyand sputum cytology.
Serumbiochemishy,includint alkalinephosphaiase.
Abdominal or whole body scans.
Faecaloccultblood.
Uinalysisfor red bloodcells.

b. Optit nmp in\)asion.wjth

sprFadof ru1loujdlono
the bdrccluroid
lo
rhe
brainrli8. 12t2Li6
?d.F
.su
c. ulfiise
tnlttation at t rereh1awj rhoui e\oph,
ti(
or endophvtjcgl.owth.
d. Me!astatiispriad*to regionalnodes.lurg,or41
In.both hedtable and non-heritabteretinoblastoma(see
below), th rjsk of_metasiaiicdiseaseis gearer {
the
tumour js advance4 and if there is reholamirur opft
ne^e invasion.massivechoroidalinva>ior1411s116,
Lhamber
m\ olvemenlandorbitalsprcad.
Repedred
recurrnces atter conseryative heatment also hdicate ar
incrasedrisk of mtastasis.

Genetics

Rtinoblastoma
results from malignanttranslormanonot
primjtiv retinal ceilsbelorefinat differentiarion.Because ,
Managenent
thsecellsdisappearwithin the first few yearcof life, dr
,
Obbrvation.
iI rhepahcntis aiymplomdliLor recei\. Lumouris.se)dom
seenaJter? yearsof ag.Rehnobldst_
in8 systenicchemotherapy.
omamay be heitabteor non-heritable.
Thegenepredis,
Radiotherapyeithere\lernalbeamor brdchyrherapy. posrngto retinobiastoma
(Rrl) is at 13q14.
TTI i. usefultor smallh)mo]lJ.with mini tsubretil. Herifable (gelmline)retinoblasromaaccountsfor 40%.
nal fluid.
An.associarion
with advancdpaterndlagesutgests
Svslemi(thrapyfor lhe pnmarytumourmayalsobe
marrn
some
patren!s
themulatjonhasoLcurred
benefi
cralfor choroidalmitastases
in tJE
father's sperm.In hedtableretinoblastomaone allele
of R8l (a tumoursuppreqsor
geneti6 mutatedin all
Dooycels. whm a turLhermutagenicevent(,second
hit') aflectsihe secondaltele,the cell rmdergoeimalig
nant transfonnation.Becauseall the retinal precurso.r:
cells contain th hitial mutation, these^childrbn
, develop bilateral and muttifocal rumours. Heritabibl
retinoblastomd
reonoDrastomd
patientsalsohaved predisposition
pahents
to I
tO
Retinoblastomais the most comrnonprimary i raocular
nonoculdrcrnceF,mosLnotablypinedlorquprasella,
malignaicy ol childhoodand accoun6for a6oui3%oI all
pnnutive neuroectodermal
tu;our fpNlt ,lso
cNldhood cance$.Evenso, it is rare, occurringin aboui
known as p;nealoblasLorMand blateral yetinoblast1:17000live birtlls.
oma).which occursin about3%. SecondnatirFant .
neoplasmsinclude osieosarcoma,
melaroma,and ,
Pathology
maiitnancies of th tEain and lun& each of thege
tumours lending to occru in a parfiiuJar age group.
1. Hislolo8y.Tte tumouriscompo.ed
ofsmal basophilic
The dsk ol secondmalignamyis abouLe% buLthis
cells(reLinoblasts)
with talsahrperchromariL
nuclei
';ednoblactomas
indeases five-fold if extemal beam inadiation nas
and scdnly cytoplacm L,lany
are
been
used to neat the original tumour,the second
undillerentiaLed
{}ig. 12.324)but varyingdeSree.ot
hrmour
tendint to arisewithin the inadiated field.
d lerenbaiionare charactenzed
by rhe formahonof
. The mutation is hansmittedin 50%but because
of
rosettes,of which there are thlee types:
incomplete
peneb.ance
only 40%of ofispringrdl
a, Eleinerwinteqteiner rosettesi;nsist of a cenrral
lumen sureunded by tall columnar cetls. The
. If a child hashedtableretinoblastoma,the risk fo
nuclej of ihe cells iie away from the lumen (Fig.
siblingsis 2% if the parentsare heatthv,and 40%
12.328).
if a parentis afIcted.
b. HoneFwight rcsetles(pseudorcsettes,)haveno
. About 15%oI patientswiih heleditar"yretinoblaslumn and the cellsform arounda tangleomassot
toma manifestunilateralinvolvement.
eosinophilicprocesses.
2,
Non-heritable
(somatic)rednoblastomaaccountsfor
c. Fkurctte are foci of tumour ce s which exhibii
50%
oI
ca.es.
Tle
tumouJ$ unilaterdi,not trdnsmisphotoreceptordifferentiation.Clusiersof cellswith
sible and doesnot predisDosethe Datimt io second
long.)loplasDi( proces\esproiect rhrouSha
nonocular cancers.It a patient has-a solitary retinorenesratedmembrane
and fie aDDearar"Lr
re.em_
blastomaand no positiv; famity history, this is prots
blesa bouquerof flowers(Frs.1i.32C).
abty but not definitelynon-heriiabtesoiiat tte lisk in
2. Pattern8of tumour spread
each
sibling and ofisiring is about 1%.
a. GrcwlhFanemma\ beendoph!,tic
{inrothe\ rtre-eedinS
ox$. wjth
of rumourcellsrluoughourthe SibLingsat dsk of retinoblastomasholld be sclemedby
eyeor exophltic (intoihe subretinatspace),causing prenatalultrasonogrrphy. bv ophrh,atmo.copi
soon
"nd
retinal detachmeni(Fig.12.32D).
dtlerbirth andtheireguidrly
unti theageof+oriyears.

Retlnoblastoma

l,',.,,

" ilii

flg12:2PatholocJ
of retrfobldstorna
turno!r;(8)wetdifferenliated
{a)undiflrentiated
turnour
showsaoundanr
fxner.
,:::lt:t.{c)
scrion
showsa mxedendoph).,ric
lD)$hoeye
(ntorhevitreoustanrr
(inro
exoph},|c
Ili"l:fli:l
le!rerles
LtsuoferndspacergroMlr
patterri
section
oflre cutendoiltreoptrcnerve
F trafsrrse
withanareaof tumoLrr
lLoria:r.rl

Balr}aic c Misson,tor Eti\i.atAphthatnnpatnahCt,Er,nennlh hcherat

2AAt tE A .aubst at t H{t!

t)*Ec,DaadEj

511

512

Prcsentalian

jr-hi^!\rnayb associatedwith pseudohpopyon (Ii&

12.33D).It is therefore important io considerretinoblastoma in the differeniial diaSnosis of urusuai
cfuonic uveitis in chil&en.
Orbitdlindamruiion (Fit 12l3E) mimicajngorbiht
or presepulcellulitjs may oc.ur wjlh necrofi. tunous.
It does not ncessarilyimply exhaocular extensioar
and the exacimechanismis not known.
Orbital invasionwith proptosisandbony involvetrnt
may occurin neglectedcases(Fig.12.330.
Metastaticdiseaseinvolving regionallymph nodesand
brain beforethedetectionof ocularinvolvementis rale.
Raisedintsacranialprcs$rle due to 'hilateral rcunoblastorna'bforeihe diagnosisof ocutarinvolvemeitl

Presentationis within the fiist vearof lile in bilatenl cases

.and around 2 yearsof ageif tie tumour is onilateral.

. Le*ocoria (white pupilary reflex - Fig. 12.334)is

the commonestpresmtation (60%)and may fust be
noticed in family photographs.
. Stmbismusis the scondmost common(20%);fundus
examination is thereforeinandatory in all casesof
childhood strabismus.
. Secondaryglaucomawhich is occasionallyassociated
with buphthalmos(Fi8.12.338).
. Diffuse relmoblastomainvading lhe anteriorsegmmt
tends to present h older chil&m. It may causa
red eyedueto tumour-induceduveitisandms nodules . Routineeraminahonof a palieni known to b at

t9
tl!.1213Presentation
of retinoblastoma.
gtaucoma
teukocoria;
andbuphthatmos;
{A unitaterat
lBlsecondary
{C)redeyedue
to weitjs;{D}i s nodules
andpseudoh}?opyon;
lq orbitatinflammationi
O orbitatinvasion
lcolnest of N RogeB- tigsA ahdB; U Raina- flA c)

513

si!.-:;
lndirect ophthalmoscopywith scleratindntaiion must
b pe omed on both eyesafter full myddasjs.This is
becatsewithoui indentationpre,equatorialtu4ours may
andoneeyemay haruourmultibemissed(Fig.12.34A)
ole l mours.The (lirx.al .igns oepenoon tumourqize
and gowth pattern.

1. Photocoagul*ion
u.rrg low.ener$ 532nn drSonor
8t0 1m diodpl.-er a(hreves
tocdlaonoidar;onarter
chemod^erapy.
At leabrthreetrearmenl.essionsare
needd,
2, Cryotherapyusingihe h.ipleIreeze+hawteclnique is
usefulfor pre,equaiorialtumours without either deep
invasionor vitreousseeding.
3. Chmothenpy wiihout 6ther heatmmr can be
attemptedfor a maculartumour, to conserveasmuch
vision as possible,bui there is an increaseddsk of
tumout rccunnce,

. An inlraretinal tumour is a homogenmus, dome_

.hdpFdwh'te lesionwhich berome.irregutar.ottm
h irh hhile necksol ca_l.rticdlion
(Fi8.t2.3ABJ.
t An mdophytjctumourproierFinto rhevjbeo!>as a
Treatnent
ofnediun.size
tunourc
white mass(Fig.123aq that may,sed,intoihe virreous(Fis.12.34D).
Tumours up to 12 mm wide and 6 rnm thick may b
' An exophytic tumour forms subretinat,multitobular hatedasfollowsl
white masses(Fig 12-34E)
andcausesoverlyingferinal
1. Brachltherapy usinSiodine-12sor ruthenium,106is
detachment
(Iig. 12.34F).
indicatedfot an aniedortumour if thereis no vrreous
seeomS.
Investigations
2, Pdmary chmothrapywith intavenous ca$oplatin
1. Red rdlex te3tin8with a dire.l ophthatmoscope
etoposideand
vincr;tine{CIV)is glvm u t}ueetosir
has
Deenrecorrm)ended
asa screenhttestin lhecommu_
cyclesaccordint.ro
thegrade of red;obtasloma
Sintte
ruty. Any as].mnehy indicatesfull eye examination
agent chemoreducLion
wirh carboplatinatone lia.
\qjth pupil dilatation and immdiate referar rc ar
recenLly
benfound ro give similarresuttsto multi_
ophthalmologist.
lh"."py. Systemic heatmnt can be suppte_
"t"rl
2. Examination under anasthEia includes the
mented with sub-Tenoncarboplatin iniections._ihis
followingi
may be followed by local treatmentwitii cryotherapy
or m to consolidatetumour control
" Ceneralexaminationfor congenitalabnormalities
of the faceand hands
3, Erlenal beamradiother.pyis avoided,iI possibte,
in
. Tonometry.
patientswith heritablererinobtastorna
bec;useof rhe
. MeasuremenloI tlte comealdiameterand,if giaurisk,ofindudnga secondrnaljgnancy.
Hypoptaeia
of
comaB presmt, the axial length of the eye.
tn DonyorbrLcano.cur,especiallv
if radrotherapy
is
. Anterior chamberexaminationwith a liand-held
admiru"stered
in ihe fust 6 nionths'oI life.
slit-lamp.
. Ophthalmoscopy,documentingaI findings with
freatment
oflargetunours
colourdrawingsor photosraDh:v.
1. Chemothenpy to sMnk the tumour (chemoreduc_
3. USisu.edmainly-to
assess
tr:iroLuitze.ltalsooerecrs
tion),Jacilirahntsubsequmtlocaltredhrent,thereby
calcificationwjthin ihe tumour (Fig. 12.35A)and is
avordrngenucteabon
or externalbeamrddio$erapy.
helpful,inLhediagnosis
of simulatinitlesionssuchas
Chemotherapywill also have a beneficialeflet if-a
snlailer tumour ic presentin the tellow eyeor if there
{. CT alsodetectsLdlcification
(Fig.12.358)
but entaijsa
rs a Putealobtastorha.
sjgmficant dose of radjarion aid b performed onJy
2. Enucleationis indicatediI thele is rubosis,\,{reous
ftrely.
haemor.hageor optic nerve inva6ion.It is also per5. MR .annotdetectcalcificarion
buLit is supefiorto C]
formed if chemoreductionfails or a normallellow eye
lor opticnerveeraluaiionanddetection
ofexhaorular
malesagFessive
chemothempy
inappropriare
and i5
exien.ionor pinaloblastoma
especially
[fi8. 12.35C),
aiso u5fui tor d;ftuse retfoliasroir'a becauseof d
wrth contlasrand tdt sLrppression.
VR may alsobe
poor \/iualprognocisandhjth risk ol recurrencewr Lh
usetulto differentiate
rerinoblasroma
Fromsimulatrng
other therapeutic
modalrties.
Enucleahon
shoujdbe
conditions.
performed w h minjmal ma pujarion and rt rs
6. SFteriic assessmentincludes physical examination
imperativeto obtaina )on8pjectof op6cnerve(12and MR scansof the orbit and 6ku1l,asa minrmumIn
l5 nm). Theorbitaiirnplantshould
beaslarg.aspor_
high-rislcdses.
U tieseindicateLhepresence
of metas;ble.Tnonrapsuleand.onjunctjvashould-be
closed
stdtjcdisease
$en bonescars,bone
nrarow arpiration
sepa]ately,
and lumbar punctue ate alsope ormed.
7, Geneticstudiesrcquire ftesh tumout tissuefrom th
Tteatnent
0fextnocular
extension
enucleatedeyeand a blood samplefor DNA analysis.
l. Adiuvant chemorherapyconsisringof a 6-month
Bloodsamplesfrom thepatieni'srelativesanda spem
courseof CEV is given ajter enucieatjon
samplefrom the fathe! may alsobe useful.
by some
cenb.esif there is reholarninal or massivechoroialal
sPead.
Tteatnent
ofsnalltunours
2. Extemal beamhdiothenpy b indicatedwhen there
Tumoursno more than 3 mm diameterand 2 nm thickrs tumoureltmsion to $e .Lrrend of rheopticnerve
nessmay be treatedas foliows:
aLenucreahon,
or exlen5ion
througl-dtes.'era,

5 1 , 1i

( , lLi rir,.r
| ()frniha{lirtrir:gl

F19.12.34
Slgnsoi retinoblastoma.
(AlSmatperipherattumour;
(B)ntraretnaiumour;(C)erdophlticturnouri{0)endoph},tic
tumo!rwjthvitreous
(tl r(ophytic
seding;
turnour;
{Rrotatretnaldelachmert
(cctiesy at B DixanFahanaffka

uas c and D: L Matteen

tiE. E)

515

Arrnr?drorhcrapy
o'. Jemrt-nr.pi.1-.orr,,*a,.,.
lo c ..olrage.r'1,
ere Ld\'tiedTa* r.ig t2 lbB)
"
tanslucent'fishflesh'mass,
anlxiureof[orh, or a flat

. New tunours candevclopin patieniswith

h tab,
rclrnoblastoma,
espcciallyihos ireatedat a very
younSa8c.
' If rednoblastoma
hasbeenharedconse aiivelyEUA
a.d1 e\cn 2 ro8 *eel- unri thedtFot.year.
i-_nF.
.r'pr wfu,h ,unFe\dmirationw thourande.rne,rd
ri
perforndevcry 6 nonths uniil the aseof about5
years.thcnannuallyuniil rhea8eof about10ycals.

Ilg,!1.35lmagirgof retinoblastoma.
{A)B scanwithtow
g,ain
showsechoesfrorncatcilicaton;
(!) axtalCTshows
0 ateralumoufsandcacfcationi{C)sagtta lvlRshowsa
pnealoblastoma
wth secondary
hydrocephalus
lclunesy0t ,{ N6char tiE.A:aD Sin1h,t'ton Ctintd A1hthatntcpathato1y,
.and.ts Etseiet,2AA7- fiq.C)

t19.12.36
BfachJ.'thempy
for retirobtastoma.
{A)Sefore
(8)'coftag+chees
treatrnenti
appearance
aftertreatment

. OrbjlalMR is indicated;nhighrisk cases

for abouti8
months.If the child has any dsk of devlopjnga
secondmaliSnantneoplasm,the parcnis shouid be
and
educated
to bealertto feaiuresof pain,lenderness
'.
rhel i-t andlo reel rredicalollmlio- J lhp,. no
improvementin a week.

Differcntial
diaEnosis
1. Prsistntantedorftal vasculature(persisienthyprplastic pdmary vitreous) is conlined to the ,nterior
segmentand often involvesihe lens
. Bseniation
(Fi8.12.37A)
dueto
is wiih leukocoria
a retrolnlal mass jnto which elongatedcjliary
p'oce5:c.drein\ened1Ii8. l2.lm dnd a)
. With time,themassconhacisandpullsthe ciliary
processescentrally so ihat they becomevisible
ihroughthepupil.
. Complications
includecataract(Fig.12.37D)for
mafiondueto a capsulardehiscence.
. Treatmentinvolving vitreoretinal surgerymay be
successfulin selectedearlycasesin salvaginSsome

Persistentposteriorftal vasculatwejs confr,]led

to
ihe posteiior segmentand th lens is usLrallyciear
. Presentatjon
is with lukocoda,strabismusor
nystagmus.
. A densefold of condensd
vitreousand renna
extendsfuomthe optic disc to the ora s(atd and
js associaied
with retinaldtachment
(Iig. 12.38).
. Treatmentis not possible.
Coats diseaseis almost always rmilaieral,upre
commonin boysand iendsto presentlater thanrcrbo.
blasioma(seeCh.13).
Rtinopathy of prrnat'rrity, if advanced,may cause
retinal detachment and lukocoria. Diagnosis is
u<udllysrraiShtforward
becarseof thehl.roryofpre
marurib and lo\abirth weight(seech. lll.
Toxo(ariasis.Chronic toxocaraendophthalmitismay
causea cycliiic membmneard a white pupil. A glanuloma at th posterior pole may resemblean endoph)tic retinoblastomaGeeCh. 14).
Uveitis may mimic the dilluse blihatinS iype of
retinoblastomaseen in older children. Conversel,
retinoblaslomamay be mistakenfor uveitis, endophthalmitisor orbitalcellulitis.

{q eafy
anterior
Persistent
fetalvasculatufe.
tlg,12.37
0) rtroentalmasswithinseltedciliaryprccesses;
lA)Lukocoria;
casewlthcataract
invoNement;
{Dladvanced

517

posterorfta vascutature
Itt.U,38Persislent

7, Vitreortinal dysplasiais causedby faulty difierenria

tion of the retinaandvitreousthat resultsin a detached
dlspjdstrcretrna(Fig.12.19A1
forminga rerrolenLdl
ma"cwilh leul,oLoriall|. t2.J9B).Other tearures
include microphihalmos,shallow antedor chamber
and elongdtedciliarv processesDysplasramay
occur in isolatjon or in associationwith systmic
abnormalitjes,most notably Nonie djsease,inconiinentja pi8menti rBlo.h Sulzbergersyndrom)a1d
WaU.rWarburgsyndrome
a, Noffie diseaseis anXL recessivedisorderin which
dff.ledmalesaJeblindai birlh or earlyinlanc).Il
tl8.12.39
Vteorelina.dysotasra.
js (ausedby muLations
specirer;
6) parhotogicat
in LheNDp geneon .h_ro- (El
clinical
appearance
mosomeXp1l. Systemicfeaturesinclude cocl eal
Gaun*y al I H.fiy andG tltksan,thn cthicatophthalnicpathaloll,
deafnessand mentalretardation.
Bu(ctuatlh.Hekenann
20A1- flg A)
b, Iflconti entia pigtfienti is an XL dominant conditjon thai is lethal i/ rtelo lor boys.Mutations have
beenfound in the Nf,MO gene on chromosome
Xq28.It is characteized
by a vesjculobutlous
rash
spontaneouslyto a calcified massassociatedwith
on the trunl and exhemiries[Fig. 12.40.4)which
\\'th tine is repla.edbv linearp)tmenLabor(Fjg.
llE.aleralon and chodoreriMtahophy (Fig.
12.41).The firul appearanceis remarkabtyiimilar
l2.a0B).Other icdture<inLtud; iralformarono,
to that of a retinoblastomafollovrins irr;diation.
teetl, hair, nails,bonesand CNS.
Rarely, a retinoma can later hans-forminro a
.. Walketwalb ry slndlome is an AR condition
rapidly gowint retinoblastoma.
characterizd
by absen.eof coriicrlgr.riandcereb. Retiftal astrocytorna,whichmay bemultilocalaad
bFllarmJfornarionsrhdLmay be d..o.iaredwiLh
bilateral (seebelow).
hydrocephaiusand mcephalocele.Neonat6tdeath
is cornmonand survivors suffer severedevelop
mental delay. Apart ftom vitreoretinat dysplasia
o.hero.uldrfeaturee
inL,udefetersdnom.r' -. rdcL,u\eal colobomr,
#';;11
Ashoc''toma of the retina and optic neru head is a
",j.."ph,n.ho,
nrve hypopiasia.
raJehamdnonu,whichdoe. not usuarl)threaten
\ision
8. ottrer tum6urs
and does not re$iire Feahnent. Most are mdophvhc,
a. Rethnfla (retinocytoma)is a benign vanant ot
p'oirud],rginto LhFviireous.but exophyticsubretinal
ltinoblastoma.It is charactedzedby a smooth, rumours can occl.u. Asbocytomas nay occasionally
dome-shapd lesion, which slowly involures be encounterdas incidental solitarv lesionsin nomat

Astrocytoma

5rB
indivjduals but are most ftequently seen in tuberous
/seebeloa)andoccd-io1,lly
s.leros.s
n asso.i"rion
wrrh
NFI andretinitis pigmenlosa.About 50%of patientswiih
tubeiolrs sclerosishav fundus ashocttomaswhich may
be multiple and bilatral.

Diagnosls
1 . Histology showsfibrillary astrocyteswith smaltoval

nucleiand cyioplasmic
processes
Fig. 12.42A).

2, Prcsentation.Most tumours ar asymptomaticanq

detectedon screeningfor tuberoussclerosis.

3, Si$s
. Yellowisl! semitansparent round plaque or
nodule(Ij8. 12.428).
Lafge.elevardmulberrylile_lesion (Fjg. 12429
that showsautofluorscence\Fjg. 12.42D).
Mued type which is seminansparentin tie periph.
ery dnd.dllfied cenirally
. Most tumourcare static,and long-standinglesions
may becornecalcified(Fig. 12.42E).
4, FA shows a Fominent superficialvascularneh.\'ork
wjthin the tumour in the
piase followed by
"rterial
ldrleakdff andstaininSfjg
1242F)

fubefous
sc/efosis

pigmenti.
tld.12.40
Incontinentia
rash;
F) Vesciculobullous
pigmentation
ln an olderchild
lB) nearcutaneous

Tuberoussclrosis(Bourneville disease)is an AD phacomatosischaracterizedby the developmenioI hamarto"

mas m multiple organ systemsftom all p mary germ
layers.Theclassicftiad of (a)epilepry,P) menlalfttardandn
and (e)\de ofia sebauumis only presentin a minority oI
patients,but is diagnostic.About 60%of casesare spcJ.
radicand40%areAD.
1. Culanouss'tru
. Adenoma sebacexm,consistingof
tous red papules with a buttdy

aroundthe nosFand cheeks,

is univer.al(
12.434).
. A.shlealspotsarehypopigmenled
on
macules
trunl (Fi8.12.438),limbs and scalp.hr iniantswith.
Bparseskin pitmentation they a;e best dtected
usjnBultsavjolet
litht, underwhichtheyllloresce
(wood tanp).
. ConJettiskin lesions.
. ShaSreen
patchesconsisiof dilfuse thickenint over l
th lumbarregion.
. Fibous plaqueson the forchead.
. Skin tags (molluscumfibrosapendulurn).
. CaJ-aulaitspots.
. Subungualhamartomas(Fig.12.43D).
Neuological features
. Inhadanial paraventricularsubepmd''nal astrc
cytic nodineaig. 12.43D)and giint ceil astocytic
. Mmtal retardation.
. Seiz$es.

Reunorna
tig,12.11

. Renalangiomyolipomasand cysts.
. Cardiacrhabdomyoma
. P monaryllmphangiomaros:s

..

.:

.,|

.?f

'

"|,

I
4

6.e

Flg.12.42
Astrocyloma.
(A)Hisio/ogy
showspfoliferat

"11ilffi
ffi'i".#;
:Hi#x;ffi
[ii""J*:
:'.:[i,t5,il:..""",
fi1,.T:T;*[:ffl
ilil1ii.i".Ul;i[["#tff

lcnunesvct
) Hanv tic A;F Giti tilscantlD)tDonalo&6a59todsreredscorr,.,4rasofrjraclrafDiseases,llosbf1997l1g.f)

t19.12.43
Tuberous
sclerosis.
sebaceum;
subungual
14Adenoma
hamartoma;
{q ashteafspot;{C1
a
0} axialCTshows
perivent
cuiatastrocytic
nodule
lcoun*y al 4 Nbchat- llE A; friAMt, 1tn Alas ot dtnhat Dta9n6k,MasW2oB - ng.B)

4, Ocular feature!, apa hom fundus asfocytomas,

includpahhy iris hypopigmentationand at)?ical i s
cotoDornas,

Diagnosrs
L lli6tologr/. The tumoui is composedoI cap
vascularchamelsbetweenlargefoamycelis
reprcsent histiocytes,endothelial cells or

(Fis.12.44A).

Capillary
haemanelioma
overview
Retinalcapillaryhaemangiomais a mre sight-tlueatening
tumour-thatmay occasionallyoccll] in isolatio& although
about50% oI patimts with solitary tesionsand virtuaiiy
all patientswith multiple Iesionshavevon Hippel-Lindau
disease07Hl - se below). fhe fievalence of retinal
tumoursin VHL is approxirnate\ 6ti%.Vascularmdothelial growil Jactor0?XGDis importantin the development
of retinal lesions.

2. Prentation.Thmedian ageat diagnosisin

with VHL is earlier(medj; 18
detected by screningof
of sFnphomsdue to maculare.(udates
or
detachmmt.
3. Signs

. An earlyhmour is a small,well'ddinedoval
iesionwithir thecapillarybedbehlreenan
ard venule (Fig.12.448).
. A well-stablishedtumout is a round or
massusuallv locatedin the suDero-or inJetoE
poral peiphery with dilatatioi and tortuoGity

.']]a.nlla

-,;nL.-

a j haemans
orn..{ajHrsrolog}
shows
capilrar},
kevascu
archanne
s brwen
arseroarny
li.:i:1 I:l* cap
cersl
n, *" rvanced
rrrnour
dssoc
ared
wrhvascurai
dratation
ano
tortuostty;
op|i
nerve
iread
lrij
teson;
3 ii l lHi,j;
isa;sDana,a
tsc;iDcnauMcass,,ah
i1iffi1,"lii3l'iiti.i,I'i,!U::{l:!;:',31iy't"f;'::l::::::::::::::!:tr,!:r,hHe,Neha'n2aaf

52\

ti supplyjng artry and draining vein extending

from the optic disc (Fig.12.44C).
. In a jurdapaPillarytumour the dilated vesslsarc
" absentor lessevident (Fig.12.44D).
. A sessiletumou is an ill-defined placoidjuxtapapillarv lesionfFis.12.44D.
(Fje.12.45A)and
FA showsarly h;pernuorscence
tareleakage(Fig.ii.+sl;. Therei. alsoraPid fillint
and e).it of dye.
Complications
. Eiudate formation in the ara flmounding the
tumour and/or at t]rc macula Fi9 7246)
. Bleedintandlealageresuidntin macularoeoemd
and exudativeretinal detadvnmt.
. Fibrotic bards, which cancausetractionalor rhgrutosellous retinal detachment.
. Vitre6us haemorhage, secondaryglaucomaand
phthisisbulbj
6. DillerentialdiagnosismcludesCoatsdjseaseretinal
rucroaieulvsm and vasoproMerativetumoul,

?leellrei,i
1, Ob3ervationis advisedfor asymptornaticjuxtapapillary haemaryiomaswithout exudatio&becausethese
may remain maciive for marry years and bcause of
the high risk of iafogenic visual loss.Early peripheral
lesionsarenot uually left untreatdbcausthy ate
relatively easyto ablate.
2, Laserphotocoagulationof smalllesions.After closinq
the feeder vessels,the tumour is treated with low:
energy,long duration buns. Multiple sessionsluy be
needed.

Cryotherapyfor larger peripheBllesionsor those .

with exudative retinal detachment.Vitorous heat-

4, Brachythenpyfor lesionstoolargefol cryotherapy.

5, Vihorctinal surgery may be rquired for nonabsorbing
vikeoushaemonhagg
epirctinalfibrcsisol
bactional retinal detachment.II appropliate,tbqJ
fi.lmourmay be d$boyed by endolaser
tion or surgicalrcrnoval.

G. Othermodaliti$ includePDT,whichavoids
io adiacenttissues,and anti-vasolar end
agmts.Theseareworth
$owth lactor(VEGF)
eringwith juxtapapillarytumows,which arc
withoutvisualloss.
wire virtuallyunbeatable

syndrcme
VonHippel-Lindau
Inheritane is AD conditionca$edby a
the\4HLgeneondromosome3p26-p25.
Oinical featureo
C.JShaemangiomainvolving the cerebellum

12.47A),
spinalcord,medullaor pol|saflcto
25%of patiertswith retinaltumours,
Phaeod|lomocytoma.

. Renalcarcinoma(Fig. 12.428)andpandeatic
cell carcinorna.
. Cysts of the te$e3, kialneys,ovaries,lun$,
and pancreas.

@
(l) Ea yfilling;
haemangioma.
tl!.1115FAof retinalcapillary
(B)late leakage
Gbunesyaf) DoMh M aast ltfi sle@copilr,4uasol A4rculrfDiwset

witha juxtapapillary
flg.12,46
Severe
exudation
associated
capillary
haemanEjoma

amin
.levls liom age 10 years to detect
phaeodtomocytoma.
b. Sdeenhg eoery2 ye4n involves abdominal and
brain tr& from the ageof 15 years.
Caned.tcslsa.reindi(arcd
in ajl parients
with sus_
pcteddjseaseand in lirst and seiond desreerelatives.Wjlh modem rechniques
Lhesensitiviryig
almost100%.

Cavernous.tT,gmangloma
Cavemoushaemangiomaof the retina ard optic nerve
head is a rare/ unilateral, congenital hamartoma.lt is
usually sporadicbut occa$ionaliycanb inhefted as AD
with incompletepenehance,in iombination with lesions
of the skin and CLlS (neurooftlocutanousphacomatosis' or 'cavemomamultiplex,),

124?Tumours
in vonHippel-Ltndau
syndrome.
0) Axial
shows
a cercbellar
haemangtoma;
IBJarialCTol the
n shows
a renalcalcinoma

1. Histolory shows multiple thin"walled dilated channels with Euface qliosis.

2. Preeentationmatbe with vitreous lBemonhage oi,
more frquently,a-Ea chance6nding.
3. Sihs
. Sessileclustersof saccu.lar
aneurysmsresembljng
a-'buch oJ_grapes'in the peripfieratretina (Fjg:
12.48Aand B\.
. Becaus
of Eluggishflow of blood,theled cellsmay
sedimmt and separatefrom plarma,giving rise tir
'mmi6ci'
or fluid levelswithin rhe k;on.
. The lesion occasionallyinvolves
the oDtic nene
head(Fie.12.48q.
4, FA nigNights.the sedimentatjonof erythocytes and
shotrs delayedfilling in the venousph;ge ana hck of
leakage(Fit, 12.48D).
5. Complicatiolr!, which are uncormor! include llaem_
orrhageand epiretinalmemtraneforrnation.
6. freatmert..Rsrly vihectomy may [e necessaryfor
non-abso$ing vib"eoushaenonhate but photocoagulation shouldbe avoidedasjt may p-recipiiate
haem"or_
'
rhageand enlaryementof the tuhi:ur.

ol cD FalDsahdutFJ.cl6an,ttuh Atas4d taxtof clhtcal

Racemose
haemangioma
. Polycythaemiawhich may be the
result oI lactors
- releasdby a cerebetlaror renal tumour.
screeningis vjtal bacauseit b impossjbleto Dredict
which patients wi6 rctirEj hjenangion;
wjU
rDibour systmdc lesion3.The ophtha.kh;loqbttrlust
thueforerefer all such patientsfor svstemicind neu_
lologjcalevaluation.Relativesshou.kiajsobe screened
bcausof the dominant inleritaffe paflem of the
drseaseTh following screeningprotocol shouJdbe
regularlyperformedin patientswith establishedVHL
a. Afinaol scteeflirrg
. Physicalexa;inarion.
' Annual ophtlDlmoscopy
from age 5 years,
hcreasedto 6-montNy hom 10 to 30 vears.
. Reral ultrasonographv
from aee16 viars.
' fwenq Jour ho-ur'urine
coleition ior estrmation of vanillyl nandelic acid and caiechol,

F.acemosehaemangjoma(also hown as arteriovenous

malJorrnation)of the retinasnd optic ne e headis a lare,
6poradrg usually unilateral, conFnital malJormahon
rnvorvrngduecl cohmuni(ation betweenthe arteriegand
veinswithoLrt.anjntemening.apillary bed.So'le patjents
nave-snurar lpsrlarenl lesionsinvolving the midhEain,
-(an
basofrontal region and posterior fossa
assocnbon
relered to as Wybum-l!{asonsynd.rome).Braininvolve_
mefi may.teact
to spontaneous
luemorrhage
or epilepsy.
Occasionally,nralfornutionsmay involve tie maxilla'ard
manorbte,predrsposlrt the patjmt to haenonhageaJter
clental heafnent. Facial skin lesions have abo been
rePorted.
l. Present.fion is usually as a chancefindins.
2- Signs
. Enlarge4 tortuous blood vessels
which are often
more numerous tllan normal with the vein and
anery appearint simitar (Fig,12.494).

521

( l l i r i r tr r ll . r rf h i h r r { i i r o i c r g r

(l) Vert sma I peripheralesion;{8)largerperiphera esion; {C)opticnerve nlolvemeft;

tlg.12.48
Cavcmolshaemangiorna.
plasma{hyprlluorescent)
l0) FAshowsllrid Levelsdue 10 separalon oi fed ce ls (hypofLrorescent)irom
Man\
1997
ti4.
D)
Danrttt
M
eass,
nai
srcn
dr^laNrar
lireases,
$rrcllrJs
Itn\fteyat)

. With time iire ressels bccone more dilatcd 1 , Histologyshorvsghalcellsanda neiworkol finecaP'
illadcswitl somlargcl dilaicdlcsscls.
and iortuous,and ma)' becomescleroiic1F18.
wrtn
Besentationjs usuallyin the 3rd-5thdecadcs
12.498).
blulTlngof visiondueio nacularexudaiion.
3. FA showshypcrfluorcscnce
of lakage
bul abscnce
Signs
(Fit.12.a9q.
. A reddish-yellowglobularvascularmass,most
4, Tleatnentis not requird.
priPhery
frequendvlocaiedin iheinJefotenpoml
(Fis.12.50).
' n"tl*t
mav bc secnenteringth lesion
",i*at
Posrenoly.
ComplicalionsincludcsubretinaleiudatioryrudaReiinalvasopfoliferative
tumour is a rarc gliovascular
tivereiinaldetaclment,
macuiaroedemaandfibrosr9
lsionwhjch canbe primaryor secondary
to conditions
slch as inte nediateuveitis,oculartraumaandretinitis
TreatnentwithiryotherapyorbrachytheraPvrduces
pjgmniosa.Scondarylesionsmat' be rnuliiple and
.egress;o"
of thetimour irid e*"datio"bui ihevis al
bilateral
dependint
on
the
undrlting
occasionally
progrosisis guardedlI ihereis maclnopathy.
aetiology.

Vasoproliferative
tumour

- - -. '!i!firi
.::4ltLtlatJ| iiittti;

flg.12.50
Vasoprol
frativetumourwilhreUnaderachmcnl

0verview
lymthorn:r is i group ol condilionscharictrriz{rdby nco_
t l . ' r . . i - r .1. t, 1. t i , r , , a . , . t i , r r h , . , I n u r . . { , . 1 . L f l
I ' u l r l v r n T h , ' J i l rl iht \ . , , r ' l . t r r t r { ,i,a- t t . , m . , , U
oc.asi(D.rlly CNS involvcmcnr. Tbo nunr chssificalion
ind ocular mirnifrsidtnrrsarc.s ft (,ws:
1. HodSkin discasc may caus. rntcrior llveitis,
vjlrjiis, and multifocai Iundus ltsjons rcstmblirg

I
flr.r? qy !d

e - 0 s 6 | d e . o . g o n d . ( A )V a i - t . . d i r c i a , o l

andtcrluosiry;
{B)moresevereeson in whtchsorne
vessesshowscerosis;(C)FAshowshyperfluorescence
bu1

2. Nonllodgkin lyn,Ihoma nray .a!se .onjlncrjrat

invoh,cm{rl, orbiraI invoivclnnr,Mi kuticzsyndromc
and uveal infiltrauon.
3. CNS B{cll lynphona may bc.ssocjatcd wlf rntnrmedlateuvciiis and subltt,I inJiliraics.
4. Primary intraoculnr lymphoDu (plOL) r.rtresentsa
subsetot prmary ftntral norvoussyslem lymphorna
(I'CNSL), which ls a vaJjani of erhan;dat non
Hodtkin lvmphona. lhc lymphoma cels are targe,
pleomorphic B lymphocytcs '!ith larSemutiilobular
nuclel, pmminenl nucloll and scanrycyloplasm(fjg
12.51A).The tumour arises hom witi;n rhe Uiaiii,
sprnri cord and hptomeninges,and has a \,cry poor
prognosis.Aboui 20% of paijnts wirh PCNSL have
ocular manilestations,which can precedeor follor
neurological invoilcmni. Mosi patients wiih ptOL
dcvelop CNS symptoms afrer a-mean detay of 29

Acub features
1. Prsentation
is in ihe 6ih-7thdcades
$iih umtaira]
floaters,blulred lision, red e)- or phorophobia,

425

,
cellswithiregulaf
laenlcleiandscanty
cytoplasmi
biopsy
shows
intraocular
llmphoma.
Ftg,U,5t
Prlmary
0)Vitrcous
infiltrates;
rctinai
detachment
subretinal
subrctinal
infltrates;
0) shallolv
0l multifocal
{0 coalescent
(coutEsyolPsnnh - fig,A;BDanab

n1sB ahdq AfLnakeclctt - llq, D)

which ftequentlybe.omesbilateralafter a vadable Neurological

featurcs
interval,
An inhacranial mass rnay causeheadache,
2. Signs
. Mild andor uveitiswiih cells,flareand keratic
personalitychange,fo.al deficit and seiztrles.
disease
lptomeningeal
maycauseneuopathy.
Preclpitates.
. Vihitis mayimpedevisualizationof thefundus.
SDinalcoid involvemmtmav causebilatelall
. Largesolid multilocalsubetinal infilhates(Fig.
andsensorydeficits.
. Abnomulilinial neurological
such
examinatio&
12.518).
. Occasionally
deposiismay
cranialnerve pakies,hemiparesisand ataoa
coalescence
of sub-RPE
. MR of head ind spine with gadolinium, which
forrna ling encirdingtheequator(Fig.12.519.
. O[hIfeaturesincluderctinal lasculrtis,vascular
detectone or more rntracranialtumourt
meningealor periventricularlesions,and/or 1oc
occlusio& exudative retinal detachmmt(Fi8.
intraduJal spinalmasses.
12.51D)
andopticatrophy.
. lack of CI4Ois animportantdiagnostic
Lumbar Dtmcture,whjch can demonstratemaq
clue,sincein
cellsin CSFin amifloftv of Datientswith abnomral
trueuveitissignificantvitdtjsfualmostalwaysaccomA positiveresultavoidsiheneedforbam oreye
paniedby CX,{O.

:. t :
lnvas",!,

. Somelesions_maybcomevirtualy
rotalty dpigmenied(Fit.12.52c).
1, IA. showsblockagewith a $anular characreristic,
due
. luxtapapiuarylsionsaie uncommon
(Fig.12.52D).
ro the presnceof sub.RPEaccumulationof rympno- 2.
Grouped CHRPE
. naious clls0eopardskin spots).
. Multiplele5.ons
organi2ed
ir d parrerrsimuldtinS
2. US may show viheous debds, elevated subretinal
iootprinL.r,bea-rract plgnentdhonl
anirndl
ofie;
lesions,retinai diachmentand thickeniry of the optic
.onnnpolo onese(toror qu.drdntof lhr rundrs
with the smailerspotsusuallytocatedlnor cen3. Cytology of vifeous samplesor subreiinatnoduies.
hally (Fig.i2.s3A).
4 , himunohistocft emistry basedon cell,surfacemarken
. Rarel) the hsons may b. oepignented
, po,dr
of the lympho.yriLproliferation,
dlloss idenrifiLdrion
bearrracks) (Fig.12.s38).
whichjs of a B<eI fypem mostpabmrs.
CNS sdeening by regular MR sc;ns is indicared.

Trealnent
t. Radiotherapyhas long bem ihe firstline tlealmmt
fo! PIOL, bui reculrenceis common ard compDca_
tions such as radiation rctinopathy and cataractcan
,. Inhaviheal methohxaie is useftrl lor recunent
disease,but dose monitoring js needed to qrcr
ocularcompljcationsard any iecunence.
3. SFtmic chemotheraf,ywith a variety of regrmes
inciuding methotrexatecan pmlonE'surviv;l in
pabentswith CNSdisease.
This-canbe"sivenin Lombinationwith whole bmin idadiation bit neurotoicity is a problem. A variety of methods hav been
developedto overcomethe blood-brain barrier. Sys"
temictreatmentis usually effctivefor ocular disease
and ihis is prefe{ed to ocular radiotherapvn sorne
centresbecausein addition to avoidine radialioninducedcomplicationsit may improve suidval Monotherapyfor PIOLr{'ith ifosfimide or trofosfamidehas
alsobeensuccessful.
4, Biologic.8enb involvin8 specificanri-Bceltmonoclonalantibodies
(suchasrituximabJ,may
represeni
a
lsetul
but probablyneed ro 6e given
roLary"lLerrarive,
Decause
ot poorpenebation
ofthe blood.bram

[picalcongenital
hypertrophy
ottheRPE
hypeltrophyof theretinalpiSmmtepithelium
:jlg*tal
lcHRPEris'i comirin benigrlesiln"xh;ch nay oe
{al firy(a/,eithersoliraryor
Fouped,or tb1a4jtirat.
It js -mporrant.
Loaiff"'6".i*J r,"*e", rieL" typ*

m.du.F ihe l.tter

IInpljcatiors.

mav have fnDorianL sy.lenuL

1. Solitary CHRPE
A flat, dark-grey or blac! round or ovat tesion
w-thweU-defined
mdr8i.,rs
usualtylocated
nearine
equator(Fi8.12.52A).
Depj$nented
lacunaeareco-nrnonCig. 12.528).

Atypical
congenltal
bypertrophy
of theRPE
S/9,?s
. Bilateralmultiple.
widetyseparated.
heqJentty
oval
or spindle-hapedlesronsot vanablesrzeasso.:areo
with-hypopi8menldrion
at one mdrgin fFit. 12.54A
. Thelesionshavea haphazard
distribution and may bc
pigmented,depigmentedor heterogeneous.

Sysfemic
associatiors
1, FaDxilial
adenornatous
potypoois(FAp)is an ADcon_
drtronchamcterized
by adenomaLous
polypsthrouth_
oul the rectum and colon which usuaitysLarrto
oev-eropln
adoles.ence
(Fit.12.54c).u Lrnftared,vir_
rualivaXpatientswiLhFAI developcarcinoma
of the
colorecLal
regionby thea8eof50 y;ars.As a resutrof
rneoomrnanL
mherilance
pattem,intensivesurveyof
Iamiry-mmberc
rs mperarive.Over 80%ot parienls
wllh I At, have afypicatCHRPElesrons,which are
preeentat birth. A positive criterion for FAp is the
presence
of at lea.!foul lesionswharever
theirsize,or
alredsttwo lesion,ofwhichone$ Iarqe.Suchfundus
lesionsin a famiiy membershouldL[erefor,arouse
suspicionof FAP but the absenceof CHRPEtesions
cloeBnot excludeFAP.
Gardnersynd$meis chdracterized
bv FAl. osteurms
ofrhe skull.mandiblednd long bonei.a,rdcuraneous
sorLhssuehrmou6sucha. eprdermoid
cl srs.lipomas
Turcot synd$me is ar AD or A-Rconditioncharactr"

hq !y .IN andtumoursof theCNS,parricularty

medrlloblastoma
and glioma.

Combined
hamartoma
of theretina

.'d lff"

Combined]lamartoma of the retina and RpE is a rare,

usuallyunilateral(ongenitalmalformadon
thatpreuuou.
ndnuy,alfecrsmies. tt usuJly o.curj sporadtcalllin
,
normalrndrlrduats
andoc(asionallv
in -Ddtients
rrth Nf2
and Goriin-coltz syndrome.

lesion;lc)largely
lesion;
pigmented
depigmented
lesion;0) partlydpigmented
cHRPE.
Flg.12.52
Solitary
0) Completely
juxiapaplllary
lesion
lD)

Histoloty shows RPE,sensoryrtina, rctinal blood

ves.els and viLreoretinalmembrdneslo varying
clegees,
Pr;entation is in late childhood or early adulthood
blurredvisionor metamorPhoP5ia.
wiLhstrabismu.,
SignB
. Deep$eyish piSmntationwith superficialwhitish
gliosis resultiry in retirul wrblling and vascular
totuosty.
. The lesion is usually juxtapapillary Fig. 12.55A),
pe papinary Fig. 12.558)or at the postedor pole
(Fi8.12.55c).
. Peipheml lesionsare uncommon(Fig.12.55D). Large lesionsmay caus'dragginS'of the disc or
macula.
. Uncommon associated findings include hard
ex'udate{ormationand occasionallychoroidaineo"
vasculadzationat the margiis of the lesion.
. Occasional associationsinclude disc pit, disc
drusenand disc coloboma.
FA shows early h'?erfluorescenceoI the vasculal
abnornrhbesand blockagebi pignrelrrf'8. 12.55E):

due tqi
late Dhaseshows intnse hvDerfluorescence

leakage(Fig.12.5sF).
5, Treatmentis notindicated.

Congenital
hanartoma
ot theRPE
Conqenitalhamartomaof the RPEis a rare mtity, usuany
inciientally diagnosed in asymptomaiic chiliren and
younSadults.
1. Signg
. "Smalt,jet-bla.k nodular lesion,with well-dfined
whichu.uaXyappearsto irvolvethefuilarargrn:,
thiciness of the rerini ard to spjl onlo the irlner
reti,'lal<urfacein a mushroomconJrgurdho-r'
. The lesion is t'?ical]y locatedimmediately aola-.
centto the fov'eolaaio t 1.5mm or le,sr ba'e

baction or centralfovealinvolvmeni.
2. Trcatment is not indicaied.

529

,Beartck,
tlg.12.t3
,potar
Grouped
CHRpE.
{A}
lesions;
lB)
Deartrack tesions
':::.;
'D
^^'
1" 't "

rerinopar'rie,
r,e rrrcdr.ec,e,
rru.m tslr
t."_:::u.o n r.di.rFno,ed
by rhFuudr\ obrencr.
T ", "q "'
o , i h e D dFr rr . p r e j e - *, . r r r r . u a r . y n p r o 1 1 . b e r o . rFig.12.5{Arrpi(a

.tri\
..
rnF Drj''r"r\ m"'ig-"-,\ i, ordf o.co.
Il
!r"r.rore
npol,nl tor .linr.idn, ro b. tarjt,a- wirh
hc._ .lr_
o r o m e ,l.o d A e ! r r h e u n d " 4 ) i - g n " t . g - , n . r
_",.) d
"lossrbte

Bilateral
diffuse
uvealmelanocvtic
Proliferation

{A)
CrRot.lBllagni,icar,o.
(ho*5
cfaracrerslc
depgmentat
onat onernafdrn:
potyposrs
lC)adenomatous

q,prorrer"rioor brrugnneiaro.yrc.
rn

:l:^I,:i'l::
rn.
ourcrchorold.

L SiSns
' V J l r i p l c n . e \ u , .et , L . r o d dj.e , r o n
r , r gl 2 < 7 1
.
y.:i^r:--:!.8'^ ,ub|Fhtu'par.^e.!h.L md)
'r,* _.",r.."rq
,o.)ri.
p-o.iJercuon,nur
MDI
navea rhcular
pattem.
l.;r1119
. . d v . - ) r a r D , ra - e o D L - r i ,
ry-orore o..urinq u5urt.v
. Exudativeretinaldeiachmenr
, D a L p n tr. r ! r \ . t e n . . o , r " r
oc.uhma.inancl l. ,
. Rapldlyde.r,etoping
cataracts.

Combined
hamartor,fa
Fl$1?,55
ofthe retinaandretinatptgment
epithetium.
tesion;(ll large
0) Smatiluxtapapi|ary
peipapilla
ry lesionwilh perphefalhardexudates;
(C)argeposterior
potetesionwith,dragging'
of theotsc;0) PefipheraL
lesion;(0 FAeadyvenousphaseshowshypedluorescence
of vascuiar
lesionsandbockagebt pgment;(I la phase
uorescence
showsintersehyperf
dueto leakage
lctuftest of B Danato nE.4 s Milenki - ti+ c; c Banl - tigsE andF)

Ilt,t2.56Col8entat ldnar.oma o! the .elira, p,pnenl

p r m eu m

Flg.r2tTtNaevls-like
lesionsin ditfuseuvealmelanocy,tic

. Virreousand anteriorchamber
ce s.
3. Investigations
! Antcrioruvealcystsand
tumou6_
r. rRC i. .everptyartenudred
. Epjsclrat
undcr photopiL
nodules.
5corop.c
.ondiljon(j
"nd
dart ddapdrion
2. U.9showsdiffusechoroidatthickeningand
is db;ormdl.
,
multiple
t LY:-ar,pw(tutp lr'a\ showete\dted
tumou.s
cereb,o.pi
nar urd proiinand lymphocytosis.
3. IRG is oftenreduced.
.. reat(h !9t an undulring malixrlarrclt.
4, Ire.rment.otBDUV p ihelf is not availabte.
Ijetection
rrognosrsror bothvjsionand lifi;s poir.
ol dn occu prjmJrymahgnnncv
mighrenableedr\
rrFatmeillo FnjlanLe
survival.Successtul
hedrmcnlor
mc unoeryrrS prlT:-ry.lunourmav b ojlowed
by
rFgre*ronot ihe BDUMpbut wrthourimpruvernenr

Melanoma-associated
retin0pathy

qancegfjoclaied
reilnopathy
Rr isrnosr,
requen

I".r:"::ll:l:"
llllixl. :","".i.".

of^mcranomd
a.sociare.r
rermopdrhy
cARbecause
thevisudtsymprom<

l:",5i*T;[i
Hy::r:#"di:!ilHrJ,;:
T#$"'?:ii:
::ri{ "d:,:",,81,T{ifitl:"tl;:iJ

y
l"::':';1';3.11*,'11."ta,hy,cA
s(oedred
wrLh(mducdt bronchiat
cdr.inoma,tollowed
Dygl,naecologicat
andbreastcancr.
.:',':
rerina.Clinicatandetecrroihvsiological
T ly.{
''Porar
l. s)'rnPtom6
cerrs
's the;i+d'etarsl
:fiX*T;iltJfif'I"
. S!ba.!te bilaleralvisuat
tossoverb_t8n,unuls.
o V\udt s].rnDtoms
precedelhe dratnoesof malig_ t
_anryrn halJLhFLdses.
*mmerins
ornickedns
rishts
usuaJly
by severalmonLhi.
l#i;:il;;;"'*'*
" iTllll: ,,f.y1rphrnomenon
.hirnnerin8
oi
or 2, Sign6
rrlcKring
xghts.
. Gradualcenhal visual
. Progressivereductjon
loss.
or \lsudl acuity, colour
.
,,?p",*. normat injtid|jy.but
rnpdrrment,gdre, phoio\en.ir\jry dnd
opric d..c
::,10_rr
cenhal
dtlpnuirion
scorornaattributed to conedvsfmcito"
and
viLreous
!"'li:jT#,#.*u,

darr.
adapranon
rurg l,
)lqlil,'191"::r
l'"iredretd
qcoto.narrnd penpheral
reducuon
oj darr.ddapLed
ard
51;..1^"L,rrl'a*"ir
los due ro rod
n8rr-aodpted
o_ware
and p_e,ervar;on
jiolj:lillgreceplof

" fJndu. olrer apDedrs

nor.nalon presentalron.
o Atte.lualeddrr"rjoles,
oDticdrscpallor ard mird
rlr-Ec'rante"cle\elopd. ihe d;erse proges.es.

oi a_ware
tuncdonr.
Bothrie amplrfude

r:#iJ,l*,:ti:"q,ili""",,itiTil:i,yf,:

, F:Jil',T;fl
H:Tlli'no'"rret''ut;a"".'