Leukocoria

Causes of Leukocoria
DIFFERENTIAL DIAGNOSIS
OF LEUKOCORIA
Cataract
Retinoblastoma
Toxocariasis
Coats disease
ROP
PHPV
Retinal detachment
Coloboma
Retinal dysplasia
Norries disease

Developmental Cataracts
Nontraumatic unilateral cataracts first detected
after 6 months of age also present special
concerns.Usually, the precise age of onset is not
known. In some cases, particularly those associated
with thinning of the posterior lens capsule (posterior
lenticonus or lentiglobus), the duration of significant
visual deprivation may have been relatively brief. A
history of recent-onset strabismus or leukocoria,
preservation of good alignment with central steady
fixation (even on a light), family photographs
documenting symmetrical red fundus reflexes, or
pediatrician's records of red reflex observation can
help to establish a good visual prognosis.

Retinoblastoma
Retinoblastoma is the most common intraocular
tumor of childhood, accounting for 1% of
childhood cancer deaths in the United States
and 5% of blindness in children. The incidence
is 1 in 15,000 to 1 in 20,000 live births.
Overall mortality from retinoblastoma
decreased from 95% a century ago. With
modern diagnostic and therapeutic advances,
the mortality rate from metastatic or recurrent
retinoblastoma has been as low as 5%.

RETINOBLASTOMA
CLINICAL
MANIFESTATIONS
Leukocoria (60%)
Strabismus (20%)

OTHER- Uveitis, Orbital

cellulitis, Hyphaema,
Heterochromia,
Glaucoma, Bupthalmos

RETINOBLASTOMA

Retinoblastoma
The disease is bilateral in approximately
30% of cases. The average age at
diagnosis is 18 months and 90% of
patients are diagnosed before the age of 3
years. Less than 10% of retinoblastoma
suffers have a family history of the
disorder, 90% of cases are sporadic. Of
the sporadic cases, the responsible
mutation is in a germ cell in 25% of cases
and in a somatic cell in 75% of cases

GENETICS
Retinoblastoma gene is a recessive oncogene of 180,000
kilobases.
Located chromosome- 13q14
Knudson two hit hypothesis:Germinal cells have one defective and one normal RB gene.
A somatic mutation results in loss of the normal RB gene and
hence retinoblastoma develops (somatic mutations occur
frequently enough in the developing retina, therefore lesions
usually affect both eyes)

In addition, the first child of a parent who had had a

unilateral retinoblastoma has a 4% chance of developing
the disease

PATHOLOGY
Arise in primitive photoreceptor cells.Characteristic histology:
Retinoblastomas are composed of poorly differentiated
neuroblastic cells 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
being eosinophilic stain pink.
Characteristic Flexner-Wintersteiner rosettes represent an
attempt at retinal differentiation. Histologically, a ring of cuboidal
cells is seen surrounding a central lumen. Cuboidal tumour cells
with basally oriented nuclei arranged around a central lumen.
Calcification is another feature of retinoblastomas, usually
occurring in necrotic areas. Calcium stains with H&E. It is worth
identifying calcium in suspect eyes by ultrasound, or CT scan to
differentiate retinoblastomas from other tumours .

PATHOLOGY

Retinoblastoma

MANAGEMENT
EMPIRICAL GENETIC COUNSELLING
ENUCLEATION
unilateral, poor visual prognosis
PLAQUE
4-12mm +/- vitreous seeding
EXTERNAL BEAM
>12mm, multiple foci, only eye
LASER
consider- indirect, xenon arc
cryotherapy if <2dd in size
CHEMOTHERAPY, if intracranial extension

Non-Retinoblastoma
Malignancies
Unfortunately, children who have genetic
retinoblastoma and survive their primary
intraocular cancer have a substantially
increased risk of death from one or more
nonretinoblastoma malignancies over the
course of their lifetimes, up to 35% of
children who have had a bliateral
retinoblastoma and external beam
radiation therapy will develop a second
cancer by age 25 years

Congenital retinal
telangiectasis (Coats'
disease)
Congenital retinal telangiectasis (Coats' disease) is an
idiopathic retinal vascular disorder that usually affects
young male patients unilaterally in their first or second
decade of life. Congenital retinal telangiectasis,
however, can affect patients of either gender and
become manifest at any age. Up to one third of
patients are older than 30 years of age at the time of
presentation.There is no defined familial inheritance.
Patients may present with decreased vision, as well as
strabismus or leukocoria in children. The hallmark
feature of congenital retinal telangiectasis is localized
fusiform aneurysmal dilations of the retinal vessels
reminiscent of tiny light bulbs

Retinal vascular anomalies

The vascular anomalies can occur anywhere in the fundus
and may involve the capillaries, arteries, and veins.
Other findings may include vascular loops and beading,
retinal neovascularization, hemorrhagic retinal
macrocysts, and segmentally dilated capillaries.
Leakage from the incompetent vasculature may lead to
retinal edema, lipid deposition, or, in severe cases, an
exudative retinal detachment.
The extent of retinal involvement is variable.
Infants and children often are more severely affected with
extensive vascular involvement and massive subretinal
lipid exudate.

Persistent hyperplastic
primary vitreous (PHPV)
Persistent hyperplastic primary vitreous (PHPV) is
a congenital anomaly in which the primary
vitreous fails to regress in utero. Highly vascular
mesenchymal tissue nurtures the developing lens
during intrauterine life. In PHPV, the mesenchymal
tissue forms a mass behind the lens.
A gray-yellow retrolental membrane may produce
leukocoria, with the subsequent suspicion of
retinoblastoma.
In PHPV, the globe is white and slightly
microphthalmic. Patients have no history of
prematurity or oxygen administration.

RETINOPATHY OF PREMATURITY
(ROP)
Vasoproliferative retinopathy affecting
premature infants exposed to high oxygen
INCIDENCE
Prematurity (<32/40)
Birth weight (30% < 1000gm affected)
Oxygen duration
90% ROP regresses spontaneously, 5%
blindness

RETINOPATHY OF PREMATURITY
(ROP)
In the early active stages of ROP, a band of
glomeruloid capillaries proliferates at the junction
between the peripheral nonperfused and the
posterior perfused retina. The proliferating vessels
break through the internal limiting membrane and
invade the vitreous, inciting fibrosis and
contraction. In the later cicatricial stages of ROP,
the retina is folded on itself by the organized
vitreous, forming a fibroneural mass that drags the
macula and optic disc temporally. The end stage of
the disease is marked by total retinal detachment,
leukocoria, blindness, and phthisis bulbi.

RETINOPATHY OF PREMATURITY
(ROP)
LOCATION
zone 1 - centred on
disc, 2x disc to fovea
distance
zone 2 - outer limit
equator temporally,
ora nasally
zone 3 - temporal
peripheral crescent
in clock hoursrush
disease- SI-SV in 2/52

CLASSIFICATION - STAGING
SI- flat demarcation line with
branching blood vessels up to line
SII- ridge with volume, blood
vessels enter ridge
SIII- ridge + extraretinal
fibrovascular proliferation
SIV- retinal detachment- a (not
involving the fovea), b (involving
the fovea)
SV- total RD, open or closed
funnel
plus disease- dilated tortuous
vessels in posterior pole, vitreous
haze and poor mydriasis

RETINOPATHY OF PREMATURITY
(ROP)
LOCATION
zone 1 - centred on
disc, 2x disc to fovea
distance
zone 2 - outer limit
equator temporally,
ora nasally
zone 3 - temporal
peripheral crescent

RETINOPATHY OF PREMATURITY
(ROP)

Toxoplasmosis
Toxoplasmosis gondii is an obligate
intracellular protozoa causing up to
50% of cases of posterior uveitis.
Ocular infection is characterised by
focal necrotising retinochoroiditis with
vitritis.In congenital infection the eye
may also be affected by cataract,
microphthalmos, and optic atrophy

Chorioretinitis and congenital

toxoplasmosis
The main clinical manifestations of the
symptomatic form of toxoplasmosis are
microcephaly or hydrocephaly, cerebral palsy,
epilepsy, mental retardation, cerebral
calcification, and chorioretinitis.
The most important signs in the diagnosis of
congenital toxoplasmosis are the three Cs:
convulsions, calcification (intracranial), and
chorioretinitis. Chorioretinitis is present in 80% of
children with congenital toxoplasmosis and is
most often bilateral; toxoplasmosis is considered
one of the most common causes of chorioretinitis.

Congenital Toxoplasmosis
Highest transmission occurs in the IIIrd trimester
90% of congenital infections have no clinical signs
Earlier infection occurs in pregnancy - worse potential
outcome
Triad:- convulsions,
cerebral calcification
and chorioretinitis
Eye - chorioretinitis, cataracts, microphthalmos,
panuveitis, optic atrophy

Investigation of Toxoplasmosis
ELISA IgM in neonates, rising IgG in adults
(although not that helpful in adults).
Fluorescein angiography (hypofluorescence in
the early stages and then progressive
leakage).
Indocyanine angiography - multiple small dark
spots may be seen around the visible lesions
implying the affected retina is greater than
apparent initially. This sign may be useful in
assessing the effect of treatment.

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.

Ocular toxocariasis
Ocular toxocariasis is a unilateral
disorder that presents as strabismus,
leukocoria or decreased vision.
Retinal damage is the result of the
host's inflammatory response to the
single infection nematode, which
must usually be dead before the
uveitis can develop. The posterior
uveitis may be of severe intensity.

Toxocariasis subretinal
granuloma
Ocular toxocariasis may present with
decreased vision, strabismus,
leukocoria, or uveitis.
Most commonly a subretinal granuloma
is present in the posterior pole in an
otherwise quiet eye.
In the early stages, it is elevated above
the retina and may resemble a
neoplasm.

Retinal detachment in
childhood
Retinal detachment in childhood can be
confused with retinoblastoma, and vice versa.
The possibility of an underlying retinoblastoma
should always be considered when a child
presents with retinal detachment and vitreous
hemorrhage, even when a history of trauma is
obtained. Appropriate preoperative studies
(ultrasonography or computed tomography)
are indicated; if vitrectomy is performed, the
specimen should be submitted for cytologic
examination.

Retinal detachment in
childhood
Retinal detachment in childhood can
be confused with retinoblastoma,
and vice versa. The possibility of an
underlying retinoblastoma should
always be considered when a child
presents with retinal detachment and
vitreous hemorrhage, even when a
history of trauma is obtained.

Norrie disease
Norrie disease, or the progressive
oculoacousticocerebral degeneration of
Norrie, is a rare, X-linked recessive heritable
disorder characterized by bilateral
leukocoria caused by retinal detachment.
Affected boys classically have a triad of
blindness, deafness, and mental
retardation. Apparent at birth or in early
infancy, the ocular findings usually progress
to phthisis bulbi. An identical disorder in a
Maltese kindred is called Episkopi blindness.

Retinal dysplasia
Retinal dysplasia and PHPV are
characteristic ocular findings in trisomy
13; in fact, trisomy 13 was called retinal
dysplasia before the chromosomal defect
was identified. The multitude of systemic
and ocular findings found in patients with
trisomy 13 may include bilateral
leukocoria. Rarely, retinal dysplasia occurs
unilaterally in the congenitally malformed
eyes of otherwise healthy persons.

COLOBOMA
OPTIC DISC COLOBOMA
Due to failure of closure of foetal fissure
inferiorly
May be isolated disc or associated
chorioretinal coloboma
ISOLATED DISC COLOBOMA
Rare,
Usually sporadic, some AD
Can be bilateral
Visual acuity varies from normal to NPL.
Associated- optic disc pit, hyaloid artery
remnant, myopia, posterior
lenticonus,transphenoidal encephalocoele,
cardiac defects, VII palsy
RETINOCHOROIDAL COLOBOMA
ASOCIATIONS
Coloboma of iris, aniridia, PHPV,
microphthalmos
Associated CVS, CNS and ear malformations

CHARGE !
CHARGE (For diagnosis at least 4 of the highlighted abnormalities are required).
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 cardiac abnormalities.
Note many other syndromes have colobomata.