Leukocoria

1
Leukocoria
2
Causes of Leukocoria

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

3
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.

4
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.

5
RETINOBLASTOMA

• CLINICAL
• MANIFESTATIONS
• Leukocoria (60)
• Strabismus (20)
•  
• OTHER- Uveitis, Orbital cellulitis, Hyphaema,
  Heterochromia, Glaucoma, Bupthalmos

6
RETINOBLASTOMA
7
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

8
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

9
(No Transcript)
10
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 HE. It is worth
  identifying calcium in suspect eyes by
  ultrasound, or CT scan to differentiate
  retinoblastomas from other tumours.

11
PATHOLOGY
12
Retinoblastoma
13
MANAGEMENT

• EMPIRICAL GENETIC COUNSELLING
• ENUCLEATION
• unilateral, poor visual prognosis
• PLAQUE
• 4-12mm /- vitreous seeding
• EXTERNAL BEAM
• gt12mm, multiple foci, only eye
• LASER
• consider- indirect, xenon arc
• cryotherapy if lt2dd in size
• CHEMOTHERAPY, if intracranial extension

14
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

15
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

16
(No Transcript)
17
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.

18
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.

19
RETINOPATHY OF PREMATURITY (ROP)

• Vasoproliferative retinopathy affecting premature
  infants exposed to high oxygen
• INCIDENCE
• Prematurity (lt32/40)
• Birth weight (30 lt 1000gm affected)
• Oxygen duration
• 90 ROP regresses spontaneously, 5 blindness

20
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.

21
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

22
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

23
(No Transcript)
24
RETINOPATHY OF PREMATURITY (ROP)
25
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

26
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.

27
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

28
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.

29
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.
  

30
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.

31
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.

32
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.

33
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.

34
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.

35
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.

36
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,transphenoid
  al encephalocoele, cardiac defects, VII palsy
• RETINOCHOROIDAL COLOBOMA
• ASOCIATIONS
• Coloboma of iris, aniridia, PHPV, microphthalmos
• Associated CVS, CNS and ear malformations

37
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.