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Leukocoria
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Causes of LeukocoriaDIFFERENTIAL DIAGNOSISOF LEUKOCORIA
CataractRetinoblastoma
Toxocariasis
Coats disease
ROP
PHPVRetinal detachment
Coloboma
Retinal dysplasia
Norries disease
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Developmental CataractsNontraumatic unilateral cataracts first detected after6 months of age also present specialconcerns.Usually, the precise age of onset is not
known. In some cases, particularly those associatedwith thinning of the posterior lens capsule (posteriorlenticonus or lentiglobus), the duration of significantvisual deprivation may have been relatively brief. Ahistory of recent-onset strabismus or leukocoria,
preservation of good alignment with central steadyfixation (even on a light), family photographsdocumenting symmetrical red fundus reflexes, orpediatrician's records of red reflex observation canhelp to establish a good visual prognosis.
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RetinoblastomaRetinoblastoma is the most common intraoculartumor of childhood, accounting for 1% of childhoodcancer deaths in the United States and 5% of
blindness in children. The incidence is 1 in 15,000 to1 in 20,000 live births.
Overall mortality from retinoblastoma decreased from95% a century ago. With modern diagnostic and
therapeutic advances, the mortality rate frommetastatic or recurrent retinoblastoma has been aslow as 5%.
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RETINOBLASTOMACLINICAL
MANIFESTATIONS
Leukocoria (60%)Strabismus (20%)
OTHER- Uveitis, Orbital
cellulitis, Hyphaema,Heterochromia,Glaucoma, Bupthalmos
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RETINOBLASTOMA
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RetinoblastomaThe disease is bilateral in approximately 30%of cases. The average age at diagnosis is 18
months and 90% of patients are diagnosedbefore the age of 3 years. Less than 10% ofretinoblastoma suffers have a family historyof the disorder, 90% of cases aresporadic.
Of the sporadiccases, the responsiblemutation is in a germ cell in 25% of casesand in a somatic cell in 75% of cases
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GENETICS
Retinoblastoma gene is a recessive oncogene of 180,000kilobases.
Located chromosome- 13q14
Knudson two hithypothesis:-Germinal cells have one defective and one normal RB gene.
A somatic mutation results in loss of the normal RB gene andhence retinoblastoma develops (somatic mutations occurfrequently enough in the developing retina, therefore lesions
usually affect both eyes)
In addition, the first child of a parent who had had a unilateralretinoblastoma has a 4% chance of developing the disease
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PATHOLOGY
Arise in primitive photoreceptor cells.Characteristic histology:
Retinoblastomas are composed of poorly differentiated neuroblasticcells with scanty cytoplasm and prominent basophilic nuclei.
The tumour proliferates rapidly, with a tendency to outgrow its blood
supply and undergo spontaneous necrosis. Necrotic tumour beingeosinophilic stain pink.
Characteristic Flexner-Wintersteiner rosettes represent an attempt atretinal differentiation. Histologically, a ring of cuboidal cells is seensurrounding a central lumen. Cuboidal tumour cells with basallyoriented nuclei arranged around a central lumen.
Calcification is another feature of retinoblastomas, usually occurring innecrotic areas. Calcium stains with H&E. It is worth identifying calciumin suspect eyes by ultrasound, or CT scan to differentiate
retinoblastomas from other tumours.
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PATHOLOGY
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Retinoblastoma
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MANAGEMENTEMPIRICAL GENETIC COUNSELLING
ENUCLEATION
unilateral, poor visual prognosis
PLAQUE4-12mm +/- vitreous seeding
EXTERNAL BEAM
>12mm, multiple foci, only eye
LASERconsider- indirect, xenon arc
cryotherapy if
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Non-Retinoblastoma
MalignanciesUnfortunately, children who have geneticretinoblastoma and survive their primaryintraocular cancer have a substantiallyincreased risk of death from one or morenonretinoblastoma malignancies over thecourse of their lifetimes, up to 35% ofchildren who have had a bliateral
retinoblastoma and external beam radiationtherapy will develop a second cancer by age25 years
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Congenital retinal
telangiectasis (Coats' disease)Congenital retinal telangiectasis (Coats' disease) is anidiopathic retinal vascular disorder that usually affectsyoung male patients unilaterally in their first or
second decade of life. Congenital retinaltelangiectasis, however, can affect patients of eithergender and become manifest at any age. Up to onethird of patients are older than 30 years of age at thetime of presentation.There is no defined familial
inheritance. Patients may present with decreasedvision, as well as strabismus or leukocoria in children.The hallmark feature of congenital retinaltelangiectasis is localized fusiform aneurysmaldilations of the retinal vessels reminiscent of tiny light
bulbs
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Retinal vascular anomaliesThe vascular anomalies can occur anywhere in the fundus andmay involve the capillaries, arteries, and veins.
Other findings may include vascular loops and beading, retinal
neovascularization, hemorrhagic retinal macrocysts, andsegmentally dilated capillaries.
Leakage from the incompetent vasculature may lead to retinaledema, lipid deposition, or, in severe cases, an exudative retinaldetachment.
The extent of retinal involvement is variable.Infants and children often are more severely affected withextensive vascular involvement and massive subretinal lipidexudate.
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Persistent hyperplastic primary
vitreous (PHPV)Persistent hyperplastic primary vitreous (PHPV) is acongenital anomaly in which the primary vitreousfails to regress in utero. Highly vascular
mesenchymal tissue nurtures the developing lensduring intrauterine life. In PHPV, the mesenchymaltissue forms a mass behind the lens.
A gray-yellow retrolental membrane may produceleukocoria, with the subsequent suspicion of
retinoblastoma.In PHPV, the globe is white and slightlymicrophthalmic. Patients have no history ofprematurity or oxygen administration.
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RETINOPATHY OF PREMATURITY (ROP)
Vasoproliferative retinopathy affectingpremature infants exposed to high oxygen
INCIDENCEPrematurity (
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RETINOPATHY OF PREMATURITY (ROP)
In the early active stages of ROP, a band ofglomeruloid capillaries proliferates at the junctionbetween the peripheral nonperfused and the
posterior perfused retina. The proliferating vesselsbreak through the internal limiting membrane andinvade the vitreous, inciting fibrosis and contraction.In the later cicatricial stages of ROP, the retina isfolded on itself by the organized vitreous, forming a
fibroneural mass that drags the macula and optic disctemporally. The end stage of the disease is markedby total retinal detachment, leukocoria, blindness,and phthisis bulbi.
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RETINOPATHY OF PREMATURITY (ROP)
LOCATION
zone 1 - centred ondisc, 2x disc to fovea
distancezone 2 - outer limitequator temporally, oranasally
zone 3 - temporalperipheral crescent
in clock hoursrushdisease- SI-SV in 2/52
CLASSIFICATION - STAGING
SI- flat demarcation line withbranching blood vessels up to line
SII- ridge with volume, blood
vessels enter ridgeSIII- ridge + extraretinalfibrovascular proliferation
SIV- retinal detachment- a (notinvolving the fovea), b (involvingthe fovea)
SV- total RD, open or closed funnelplus disease- dilated tortuousvessels in posterior pole, vitreoushaze and poor mydriasis
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RETINOPATHY OF PREMATURITY (ROP)
LOCATION
zone 1 - centred ondisc, 2x disc to foveadistance
zone 2 - outer limitequator temporally, oranasally
zone 3 - temporalperipheral crescent
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RETINOPATHY OF PREMATURITY (ROP)
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Toxoplasmosis
Toxoplasmosis gondii is an obligateintracellular protozoa causing up to50% of cases of posterior uveitis.
Ocular infection is characterised byfocal necrotising retinochoroiditis withvitritis.In congenital infection the eye
may also be affected by cataract,microphthalmos, and optic atrophy
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Chorioretinitis and congenital
toxoplasmosisThe main clinical manifestations of the symptomaticform of toxoplasmosis are microcephaly orhydrocephaly, cerebral palsy, epilepsy, mental
retardation, cerebral calcification, and chorioretinitis.The most important signs in the diagnosis ofcongenital toxoplasmosis are the three Cs:convulsions, calcification (intracranial), andchorioretinitis. Chorioretinitis is present in 80% of
children with congenital toxoplasmosis and is mostoften bilateral; toxoplasmosis is considered one ofthe most common causes of chorioretinitis.
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Congenital Toxoplasmosis
Highest transmission occurs in the IIIrd trimester
90% of congenital infections have no clinical signsEarlier infection occurs in pregnancy - worse potentialoutcome
Triad:- convulsions,
cerebral calcification
and chorioretinitis
Eye - chorioretinitis, cataracts, microphthalmos,panuveitis, optic atrophy
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Investigation of
ToxoplasmosisELISA IgM in neonates, rising IgG in adults
(although not that helpful in adults).
Fluorescein angiography (hypofluorescencein the early stages and then progressiveleakage).
Indocyanine angiography - multiple small
dark spots may be seen around the visiblelesions implying the affected retina is greaterthan apparent initially. This sign may beuseful in assessing the effect of treatment.
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Some indications for active
treatment of toxoplasmosis
Lesions that involve the macula,
papillomacular bundle or optic disc
Large, active lesions should be treated.
Immunocompromised patients should
be treated.
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Ocular toxocariasisOcular toxocariasis is a unilateraldisorder that presents as strabismus,
leukocoria or decreased vision. Retinaldamage is the result of the host'sinflammatory response to the singleinfection nematode, which must usually
be dead before the uveitis can develop.The posterior uveitis may be of severeintensity.
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Toxocariasis subretinal granulomaOcular toxocariasis may present withdecreased vision, strabismus, leukocoria, or
uveitis.Most commonly a subretinal granuloma ispresent in the posterior pole in an otherwisequiet eye.
In the early stages, it is elevated above theretina and may resemble a neoplasm.
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Retinal detachment in childhoodRetinal detachment in childhood can be confusedwith retinoblastoma, and vice versa. The possibility ofan underlying retinoblastoma should always be
considered when a child presents with retinaldetachment and vitreous hemorrhage, even when ahistory of trauma is obtained. Appropriatepreoperative studies (ultrasonography or computed
tomography) are indicated; if vitrectomy isperformed, the specimen should be submitted forcytologic examination.
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Retinal detachment in
childhoodRetinal detachment in childhood can beconfused with retinoblastoma, and vice
versa. The possibility of an underlyingretinoblastoma should always beconsidered when a child presents with
retinal detachment and vitreoushemorrhage, even when a history oftrauma is obtained.
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Norrie diseaseNorrie disease, or the progressiveoculoacousticocerebral degeneration ofNorrie, is a rare, X-linked recessive heritable
disorder characterized by bilateral leukocoriacaused by retinal detachment. Affected boysclassically have a triad of blindness, deafness,and mental retardation. Apparent at birth or
in early infancy, the ocular findings usuallyprogress to phthisis bulbi. An identicaldisorder in a Maltese kindred is calledEpiskopi blindness.
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Retinal dysplasiaRetinal dysplasia and PHPV are characteristicocular findings in trisomy 13; in fact, trisomy13 was called retinal dysplasia before the
chromosomal defect was identified. Themultitude of systemic and ocular findingsfound in patients with trisomy 13 may includebilateral leukocoria. Rarely, retinal dysplasia
occurs unilaterally in the congenitallymalformed eyes of otherwise healthypersons.
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COLOBOMAOPTIC DISC COLOBOMA
Due to failure of closure of foetal fissureinferiorly
May be isolated disc or associated chorioretinalcoloboma
ISOLATED DISC COLOBOMARare,
Usually sporadic, some AD
Can be bilateral
Visual acuity varies from normal to NPL.
Associated- optic disc pit, hyaloid arteryremnant, myopia, posteriorlenticonus,transphenoidal encephalocoele,cardiac defects, VII palsy
RETINOCHOROIDAL COLOBOMA
ASOCIATIONS
Coloboma of iris, aniridia, PHPV,microphthalmos
Associated CVS, CNS and ear malformations
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CHARGE !CHARGE (For diagnosis at least 4 of the highlighted abnormalities arerequired).Colobomas,
Heart defects,
Choanal Atresia,
Retarded growth,
Genital abnormalities,
Ear abnormalities
CHARGE is also associated with facial palsy, micrognathia, cleft palate,pharyngeal incompetence, tracheo-oesophageal fistula, renal and cardiacabnormalities.
Note many other syndromes have colobomata.