**18. Retinoblastoma**

Retinoblastoma (RB) is the most common intraocular malignancy of the childhood, occurring in about in 1/15.000 to 20.000 live births. The tumor develops from the immature retina.

#### **18.1 Inheritance**

RB occurs in hereditary and nonhereditary forms. It can be unilateral or bilateral. The hereditary form is usually bilateral and multifocal, whereas the nonhereditary form is unilateral and unifocal. The RB gene is recognized to be a recessive suppresser gene located on chromosome 13 at the 13q14 segment and some affected children have other systemic features of the 13 q deletion syndrome. It is accepted that all bilateral and familial cases of RB will manifest a germline mutation, whereas only 10–15% of unilateral sporadic cases will show germline mutation (Shields, 2006).

#### **18.2 Symptoms and diagnosis**

RB usually diagnosed between 3 months and 3 years of age, but it can be congenital or it can occur in older children. The affected child usually presents with leukocoria and/or strabismus. More advanced tumors can cause painful secondary glaucoma or signs of orbital cellulitis. The diagnosis of RB is best made by slit lamp bio-microscopy and indirect ophthalmoscopy. Ancillary studies are ultrasonography and computed tomography. The red-reflex examination is the best way to screen for retinoblastoma.

Pediatric Ophthalmology / Eye and Disorders 25

The mucopolysaaharidoses (Hurler syndrome, Schie syndrome, Hunter's syndrome, Sanfippo's syndrome): The principal ophthalmic manifestations are progressive corneal clouding, pigmentary retinal degeneration, optic atrophy, sometimes papilloedema and in

The gangliosidoses: Defects in lysosomal degradation of gangliosides can result in abnormal accumulation of these lipids. (Infantile, late infantile/Juvenile GM, Tay-Sachs disease) The principal ophthalmic manifestations are macular cherry red spot, tortiosity of retinal vessels, retinal hemorrhages and optic atrophy. Strabismus, nystagmus and mild corneal cloudy can

Niemann-Pick disease: The principal ophthalmic manifestations are macular cherry red

Gaucher's disease: The principal ophthalmic manifestations are ocular lesions resembling

Albinism: Genetic disorders of melanin synthesis. The principal ophthalmic manifestations are retinal hypopigmentation, foveal hypoplasia, misrouting of optic nerve fibers at the chiasm with altered visual function, iris hypopigmentation, photophobia, nystagmus,

Angioid streaks (blood vessel-like) and visual loss may occur in pseudoxantoma elasticum

Stretchable lids, retinal detachment and blue sclera have been reported in Ehler Danlos syndrome (EDS). Subluxation of crystalline lens, strabismus and retinal detachment may be

Ocular traumas in childhood are frequent and major causes of visual impairment, especially of unilateral non-congenital blindness in this age group. The frequency of eye traumas is almost double in boys especially in older age groups. This may be due to boys being more adventurous and aggressive. The 0-5 years of age group was at greatest risk regardless of

Galactosemia: The principal ophthalmic manifestation is cataract (Martyn, 2006).

certain cases glaucoma.

spot, mild corneal haze and fine lens opacities.

strabismus and high refractive errors.

**19.3 Connective tissue disorders** 

Fig. 9. Blue sclera in a case of EDS

**20. Ocular trauma in children** 

gender.

seen in Marfan syndrome (Traboulski, 2006)

pinguecula, paralytic strabismus and corneal opacities

be seen.

Fig. 8. Leukocoria due to RB

#### **18.3 Metastatic spread and second primary malignancies**

Metastatic spread is to regional nodes, lung, brain and bone. Second non-ocular cancers are leading cause of death in patients with the familial form of RB. Most common second tumors are soft tissue sarcoma, osteogenic sarcoma of the skull or the long bones, primitive neuroectodermal brain tumor and cutaneous melanoma. Trilateral RB refers to bilateral retinoblastoma associated with an intracranial primitive neuroectodermal tumor in the pineal or supraseller region (Murphree, 2006).

#### **18.4 Current management of RB**

Goals of treatment from most to least important ranking are: saving life, maintaining the eye and vision, and preserving cosmetic appearance. RB treatment typically requires the cooperation of an ophthalmic oncologist, pediatric oncologist and radiation therapist. Treatment varies depending on the number, size, and location of the tumors. Protocols are currently being evaluated to use chemoreduction therapy to shrink the RB in order to treat them with thermotherapy, laser therapy, cryotherapy, and local episcleral plaque radiation. More advanced tumors are managed by enucleation. External beam radiotherapy is typically reserved for eyes that fail the above methods, especially if retinoblastoma is bilateral. Lifelong monitoring is important to diagnose second primary tumor in the healthy eye as early as possible (Valenzuela, 2011).

#### **19. Systemic disease and eye in children**

#### **19.1 Intrauterine infections**

Congenital toxoplasmosis, cytomegalovirus, herpes simplex, lymphocytic choriomeningitis virus, varicella–zoster virus, West Nile virus infections are main intrauterine infections that may result in ocular pathologies. The principal ophthalmic manifestations are chorioretinal scar or an active chorioretinitis, and congenital cataract. When they are present in congenital toxoplasmosis, herpes simplex, and cytomegalovirus, they are associated with extensive eye involvement (Mets, MB. & Kumar, 2006).

#### **19.2 Metabolic disease**

Disorders of copper metabolism: Wilson's disease. The principal ophthalmic manifestations are Kayser-Fleischer ring, due to copper deposition in Descemet's membrane and sunflower cataract.

Metastatic spread is to regional nodes, lung, brain and bone. Second non-ocular cancers are leading cause of death in patients with the familial form of RB. Most common second tumors are soft tissue sarcoma, osteogenic sarcoma of the skull or the long bones, primitive neuroectodermal brain tumor and cutaneous melanoma. Trilateral RB refers to bilateral retinoblastoma associated with an intracranial primitive neuroectodermal tumor in the

Goals of treatment from most to least important ranking are: saving life, maintaining the eye and vision, and preserving cosmetic appearance. RB treatment typically requires the cooperation of an ophthalmic oncologist, pediatric oncologist and radiation therapist. Treatment varies depending on the number, size, and location of the tumors. Protocols are currently being evaluated to use chemoreduction therapy to shrink the RB in order to treat them with thermotherapy, laser therapy, cryotherapy, and local episcleral plaque radiation. More advanced tumors are managed by enucleation. External beam radiotherapy is typically reserved for eyes that fail the above methods, especially if retinoblastoma is bilateral. Lifelong monitoring is important to diagnose second primary tumor in the healthy

Congenital toxoplasmosis, cytomegalovirus, herpes simplex, lymphocytic choriomeningitis virus, varicella–zoster virus, West Nile virus infections are main intrauterine infections that may result in ocular pathologies. The principal ophthalmic manifestations are chorioretinal scar or an active chorioretinitis, and congenital cataract. When they are present in congenital toxoplasmosis, herpes simplex, and cytomegalovirus, they are associated with extensive eye

Disorders of copper metabolism: Wilson's disease. The principal ophthalmic manifestations are Kayser-Fleischer ring, due to copper deposition in Descemet's membrane and sun-

Fig. 8. Leukocoria due to RB

**18.3 Metastatic spread and second primary malignancies** 

pineal or supraseller region (Murphree, 2006).

eye as early as possible (Valenzuela, 2011).

involvement (Mets, MB. & Kumar, 2006).

**19.1 Intrauterine infections** 

**19.2 Metabolic disease** 

flower cataract.

**19. Systemic disease and eye in children** 

**18.4 Current management of RB** 

The mucopolysaaharidoses (Hurler syndrome, Schie syndrome, Hunter's syndrome, Sanfippo's syndrome): The principal ophthalmic manifestations are progressive corneal clouding, pigmentary retinal degeneration, optic atrophy, sometimes papilloedema and in certain cases glaucoma.

The gangliosidoses: Defects in lysosomal degradation of gangliosides can result in abnormal accumulation of these lipids. (Infantile, late infantile/Juvenile GM, Tay-Sachs disease) The principal ophthalmic manifestations are macular cherry red spot, tortiosity of retinal vessels, retinal hemorrhages and optic atrophy. Strabismus, nystagmus and mild corneal cloudy can be seen.

Niemann-Pick disease: The principal ophthalmic manifestations are macular cherry red spot, mild corneal haze and fine lens opacities.

Gaucher's disease: The principal ophthalmic manifestations are ocular lesions resembling pinguecula, paralytic strabismus and corneal opacities

Albinism: Genetic disorders of melanin synthesis. The principal ophthalmic manifestations are retinal hypopigmentation, foveal hypoplasia, misrouting of optic nerve fibers at the chiasm with altered visual function, iris hypopigmentation, photophobia, nystagmus, strabismus and high refractive errors.

Galactosemia: The principal ophthalmic manifestation is cataract (Martyn, 2006).
