1. Dr Mahmood Fauzi ASSIST PROF OPHTHALMOLOGY AL MAAREFA COLLEGE

2.  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.  The parents of this 18-month-old child noticed a difference between the two eyes in a family photograph and alerted their pediatrician. The child was subsequently referred to an ophthalmologist and diagnosed with retinoblastoma in the left eye, which is directly visible through the pupil as an abnormal white reflex.

4.  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.

5.  DIFFERENTIAL DIAGNOSIS OF LEUKOCORIA  Cataract  Retinoblastoma  Toxocariasis  Coat´s disease  ROP  PHPV  Retinal detachment  Coloboma  Retinal dysplasia  Norrie´s disease

6.  Retinoblastoma is the most common intraocular tumor of childhood, accounting for 1% of childhood cancer deaths and 5% of blindness in children.  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%.

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

8.  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

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

11. Advanced Endophytic Retinoblastoma Friable white mass Cottage cheese appearance Fine surface blood vesselsVitreous seedings

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

13.  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

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

16.  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.

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

19. AdvantagesDisadvantages 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. ChemotherapyAfter 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. EnucleationThis 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.

20.  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.

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

22.  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.

23.  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.

24. RETINOPATHY OF PREMATURITY (ROP) Stages Ophthalmological Findings 1 Distinct line between vascularized and avascularized region of retina 2 The line noted in stage 1 gains both depth and hight 3 Vessels extend beyond the retina into the viterious 4 Partial retinal detachment 5 Complete retinal detacchment

25.  LOCATION  zone 1 - centred on disc, 2x disc to fovea distance  zone 2 - outer limit equator temporally, ora nasally  zone 3 - temporal peripheral crescent –

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

28.  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.

29.  Idiopathic Retinal vascular disorder  Usually affects young male patients unilaterally in their first or second decade of life.  Up to 1/3 rd 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

31.  occur anywhere in the fundus and may involve capillaries, arteries, and veins.  include vascular loops,beading, retinal neovascularization, hemorrhagic retinal macrocysts, and segmentally dilated capillaries.  Leakage from 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.

32.  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.

33.  Toxoplasmosis gondii -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.  The eye may also be affected by cataract, microphthalmos, and optic atrophy convulsions calcification (intracranial) Chorio retinitis

34.  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.

35. 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.

36.  Lesions that involve macula or optic disc  Large, active lesions.  Immuno compromised patients.

37.  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

38.  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.

39.  ■ Retinopathy of prematurity  ■ Systemic diseases  Incontinentia pigmenti  Familial exudative vitreoretinopathy  ■ Trauma  ■ Toxocara  ■ Coat’s disease

40.  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.

41.  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.

42. COLOBOMA Greek word koloboma meaning mutilated or curtailed. Occurs due to failure of closure of choroidal fissure Types  Coloboma of eyelid:  Coloboma (iris):  Coloboma of eye lens:  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.

44. Eye examination for infants and children

46. 1- History 2- Complete ocular examination 3- B Scan ultrasonoghraphy 4- Intravenous fluorescein angiogram (coats disease, ROP, retinoblastoma ) 5- CT or MRI 6- Serum ELISA 7- Anterior chamber paracentesis (Anterior chamber paracentesis in a patients with a retinoblastoma can possibly led to tumor cell dissemination 8-EUA

47. Leucokoria-Key points ■ The term leukocoria means "white pupil" and is the name given to the clinical finding of a white pupillary reflex. Evaluation for leukocoria is part of the routine visual examination performed by the primary care practitioner at health maintenance visits. ■ All children with newly discovered leukocoria should promptly be referred to an ophthalmologist to exclude retinoblastoma and other life- or sight-threatening conditions. When possible, this consultation should occur within one week of suspected diagnosis. ■ 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. ■ 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, pica, geophagia, medications), 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. ■ The physical examination of the child with leukocoria should include evaluation for additional signs of the various conditions associated with leukocoria. Areas that require particular attention include dysmorphic features, growth parameters, signs of coagulopathy or trauma, and organomegaly. ■ Ophthalmic ultrasound is sometimes used to determine the presence or absence of intraocular calcium (indicative of retinoblastoma). Patients with suspected retinoblastoma require further radiologic evaluation. ■ Laboratory evaluation of the child with leukocoria should be directed by the history and physical examination findings, but may include serology or other testing for congenital infections, metabolic studies (eg. for galactosemia), and genetic studies for various syndromes (e.g., Turner syndrome).

48.  http://www.aapos.org/terms/conditions/67 http://www.aapos.org/terms/conditions/67  http://www.uptodate.com/contents/appro ach-to-the-child-with-leukocoria http://www.uptodate.com/contents/appro ach-to-the-child-with-leukocoria  http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2704541/ http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2704541/