1. Dr Mahmood Fauzi ASSIST PROF OPHTHALMOLOGY AL MAAREFA COLLEGE
Leocokoria
Dr Mahmood Fauzi ASSIST PROF OPHTHALMOLOGY AL MAAREFA COLLEGE

2. Objectives Define leucokoria Explain presenting sign of leucokoria
Enlist differential diagnoses of leucokoria
Summarize clinical presentation ,diagnoses and management of some common causes of leucokoria-
Retinoblastoma,retinopathy of prematurity ,congenital cataracts,coats disease ,toxoplasmoses,retinal detachment dysplasia, coloboma.
Outline diagnostic Workup in a child with leucokoria

3. Leukocoria
The term leukocoria means "white pupil" and is the name given to the clinical finding of a white pupillary reflex.
While occasionally the reflection of a normal optic disc, leukocoria can also be caused by abnormalities in the lens, vitreous, or retina.
It can be the initial manifestation of a wide spectrum of intraocular and systemic disease processes, and the presenting sign of abusive head trauma.

4. Causes of Leukocoria DIFFERENTIAL DIAGNOSIS OF LEUKOCORIA Cataract
Retinoblastoma
Retinal detachment
ROP
PHPV
Coat´s disease
Toxocariasis
Coloboma
Retinal dysplasia
Norrie´s disease

5. Retinoblastoma
Retinoblastoma is the most common and rapidly developing intraocular tumor of childhood, accounting for 1% of childhood cancer deaths and 5% of blindness in children.
Develops in the cells of the retina in childhood(1-4) year. Approximately 1in 20,000 birth
The disease is bilateral in approximately 30% of cases.
Overall mortality from retinoblastoma is now decreased.
With modern diagnostic and therapeutic advances, the mortality rate from metastatic or recurrent retinoblastoma has been as low as 5%.

6. RETINOBLASTOMA Leukocoria (60%) Strabismus (20%) OTHER - Uveitis,
CLINICAL MANIFESTATIONS
Leukocoria (60%)
Strabismus (20%)
OTHER -
Uveitis,
Orbital cellulitis,
Hyphaema,
Heterochromia,
Glaucoma,
Bupthalmos

7. Presentations of Retinoblastoma
Leukocoria - 60%
Strabismus - 20%
Secondary glaucoma
Anterior segment invasion
Orbital inflammation
Orbital invasion

8. Rb- GENETICS
Less than 10% of retinoblastoma suffers have a family history of the disorder(Rb gene), 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

9. RETINOBLASTOMA

10. Advanced Endophytic Retinoblastoma
Friable white mass
Cottage cheese appearance
Fine surface blood vessels
Vitreous seedings

11. Exophytic Retinoblastoma
Multilobulated white mass with
overlying retinal detachment
May be difficult to visualize through deep detachment

12. Diagnosis
Eye exam. For a more thorough exam, anesthetics may be used to keep the child still.
Imaging tests. Imaging tests include ultrasound, computerized tomography (CT) scan and magnetic resonance imaging (MRI), among others.
Consulting with other doctors. oncologist, genetic counselor or a surgeon
Biopsies are not usually done to diagnose retinoblastoma because
It can be recognized with great accuracy just by examination
A biopsy cannot be done easily without harming the eye
Biopsy may risk spreading cancer cells

13. Ultrasound

14. CT diagnosis of retinoblastoma
Calcification
Optic nerve involvement
Orbital and CNS extension
Pinealoblastoma

15. Characteristic histo pathology
Arise in primitive photoreceptor cells.
poorly differentiated neuroblastic cells with scanty cytoplasm and prominent basophilic nuclei.
Necrotic tumour , Cuboidal tumour cells
Characteristic Flexner-Wintersteiner rosettes represent an attempt at retinal differentiation.
 Calcification, 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 retino-blastomas from other tumors.

17. Management-retinoblastoma
Genetic Counseling
Treatment of small (3 mm diameter) tumours
Photocoagulation
Cryotherapy
Chemotherapy
Medium sized (upto 12 mm) tumours
External beam radiation
Large tumours
Enucleation
Extraocular extension
Radiotherapy
Metastatic Disease
High dose chemotherapy
Intra-thecal chemotherapy
Total body radiotherapy

18. Management of retinoblastoma
Advantages
Disadvantages
Photocoagulation (Laser Therapy)
The laser beam focuses on the cancerous tumor, cuts off blood supply to the tumor and shrinks it.
Depending on the size of the tumor, chemotherapy may be needed for larger tumors that cannot be shrunk just by laser.
Cryotherapy (Freezing Treatment)
The tumor is frozen and thawed several times by a cold gas and this causes the tumor to shrink.
The tumor will leave a pigmented scar and the eye lid will swell for a couple of days.
Chemotherapy
After the extensive cycles of chemo, the cancer cells are reduced, thereby, shrinking of the tumor.
There are several cycles, and there is an IV port necessary to draw blood, and inject the drugs.
Enucleation
This is removal of the eyeball and the tumor is extracted when no other option is possible due to the size of the tumor.
The whole eyeball is removed with the attendant problems of anophthalmic socket.

19. Follow-up
Heritable Retinoblastoma patients can develop recurrences and need to be followed up regularly
Examine the patients every 6 months till the age of 5 years and then annually till the age of 10 years.

20. Poor Prognostic Factors
Optic nerve involvement
Choroidal invasion
Large tumour
Bilateral involvement
Anterior location
Poor cellular differentiation
Older children

21. 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) is a serious vaso-proliferative disorder that affects extremely premature infants. Retinopathy of prematurity often regresses or heals but can lead to severe visual impairment or blindness. Significant retinopathy of prematurity can lead to lifelong disabilities for the smallest survivors of neonatal ICUs (NICUs). It remains a serious problem despite striking advances in neonatology.

22. Patho-physiology-RETINOPATHY OF PREMATURITY (ROP)
Increased oxygen increases VGEF (vascular endothelial growth factor) which promotes angiogenesis.
The proliferating vessels invade the vitreous, inciting fibrosis and contraction.
In the later cicatricial stages of ROP, the retina is folded on itself, 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.

23. RETINOPATHY OF PREMATURITY (ROP) Stages Ophthalmological Findings Distinct line between vascularized and avascularized region of retina The line noted in stage 1 gains both depth and hight Vessels extend beyond the retina into the viterious Partial retinal detachment Complete retinal detacchment

24. 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 –

25. extraretinal fibrovascular proliferation
Regressing ROP
Marked “plus” disease.
retinal detachment. Stage 4 ROP
extraretinal fibrovascular proliferation

26. Developmental Cataracts
Non-traumatic unilateral cataracts first detected after 6 months of age.
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 paediatrician's records of red reflex observation can help to establish a good visual prognosis.

27. Congenital retinal telangiectasis (Coats' disease)
Idiopathic Retinal vascular disorder
Usually affects young male patients unilaterally in their first or second decade of life.
Up to 1/3rd of patients are >30 years at time of presentation.
No defined familial inheritance.
Presentation- 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
…….

30. Pathogenesis and Treatment
Pathogenesis: Coats' disease result from breakdown of t blood-retinal barrier in the endothelial cell, resulting in leakage of blood products containing cholesterol crystals and lipid-laden macrophages into the retina and subretinal space. Accumulation of this proteinaceous exudate thickens the retina, leading to massive, exudative retinal detachment.
Treatment:
 Laser surgery or cryotherapy(freezing) can be used to destroy the abnormal blood vessels, thus halting progression of the disease. if leaking blood vessels are clustered around the optic nerve, this treatment is not recommended as accidental damage to the nerve itself can result in permanent blindness.

31. Persistent hyperplastic primary vitreous (PHPV)
Congenital anomaly in which the primary vitreous fails to regress in utero.
Highly vascular mesenchymal tissue forms a mass behind the lens.
A grey-yellow retro-lental membrane may produce leukocoria.
The globe is white and slightly micro-ophthalmic.
Patients have no history of prematurity or oxygen administration.
PHPV are mostly unilateral and non-hereditary. When bilateral, PHPV may follow autosomalrecessive or autosomaldominant  inheritance pattern.

32. Toxoplasmosis
Toxoplasmosis gondi -protozoa causing up to 50% cases of posterior uveitis.
Ocular infection is characterized by focal necrotizing retinochoroiditis with vitritis.
In congenital infection (Highest transmission occurs in the IIIrd trimester)
The most important signs in the diagnosis of congenital toxoplasmosis are the three Cs. (Convulsions, calcification (intracranial), Chorio retinitis)
The eye may also be affected by cataract, microphthalmos, and optic atrophy

33. Congenital Toxoplasmosis 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.

34. 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 seen around the visible lesions. This sign may be useful in assessing the effect of treatment.

35. Indications For Active Treatment of Toxoplasmosis
Lesions that involve macula or optic disc
Large, active lesions.
Immuno compromised patients.
Treatment with antiparasitic drugs is effective for active infections but not for the encysted form. The classic treatment includes triple drug therapy with pyrimethamine (0.5-1 mg/kg/d), sulfadiazine ( mg/kg/d), and prednisone. Concurrent folinic acid helps to minimize bone marrow toxicity produced by the pyrimethamine.
Prevention of fetal infection in maternal  Toxoplasma  during pregnancy is spiramycin. A 60% decrease has been reported in the congenital infection rate in patients who received this treatment;

36. Ocular toxocariasis infection nematode presents as strabismus,
leukocoria,
severe posterior uveitis,
subretinal granuloma present in the posterior pole
decreased vision.
Retinal damage as a result of inflammatory response

37. 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 haemorrhage, even when a history of trauma is obtained.

38. Causes of Retinal Detachment in Children
■ Retinopathy of prematurity
■ Systemic diseases
Incontinentia pigmenti
Familial exudative vitreoretinopathy
■ Trauma
■ Toxocara
■ Coat’s disease

39. Norrie disease
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.
usually progress to phthisis bulbi.

40. Retinal dysplasia Characteristic Ocular Findings in Trisomy 13
May present with bilateral Leukocoria.
Rarely, retinal dysplasia occurs unilaterally in the congenitally malformed eyes of otherwise healthy persons.

41. COLOBOMA Greek word koloboma meaning mutilated or curtailed.
Occurs due to failure of closure of choroidal fissure
Coloboma of optic disc:
Coloboma of choroid and retina:
Coloboma of macula:
Associations 
CHARGE Syndrome,Trisomy 13 (Patau syndrome) Trisomy 18 (Edwards syndrome),Cat-eye syndrome
Posteriorly located coloboma can involve the optic nerve, retina, and choroid.
If the retina is involved, it appears as an area of whitening often with pigment deposition at the junction of the coloboma and normal retina.
patients with coloboma have increased risk for retinal detachment.

42. All children with newly discovered leukocoria should be referred promptly to an ophthalmologist to exclude retinoblastoma and other life- or sight-threatening conditions

43. Eye examination for infants and children

45. Leucokoria-Key points
■The term leukocoria means "white pupil" or clinical finding of a white pupillary reflex.
■All children with newly discovered leukocoria should promptly be referred to an ophthalmologist to exclude retinoblastoma and other life- or sight-threatening conditions.
■leukocoria can also be caused by abnormalities in the lens, occasionally the reflection of a normal optic disc, vitreous, or retina. It can be the initial manifestation of a wide spectrum of intraocular and systemic disease processes, and the presenting sign of abusive head trauma.
■The history for the child with leukocoria should include prenatal exposures (toxins, infection, medications) and complications, birth history, postnatal course (infection, oxygen exposure, medications), medical history, recent exposures (puppies, kittens) family history (particularly for retinoblastoma or other eye tumors, eye loss, osteogenic sarcoma, and fetal loss or miscarriage), growth pattern, development, and review of systems.
■Ophthalmic ultrasound is sometimes used to determine the presence or absence of intraocular calcium (indicative of retinoblastoma).
■Laboratory evaluation of the child with leukocoria should be directed by the history and physical examination findings, may include serology or other testing for congenital infections, metabolic studies (eg. for galactosemia), and genetic studies for various syndromes (e.g., Turner syndrome).

46. Resources http://www.aapos.org/terms/conditions/67