Masquerade syndromes

Retinoblastoma

CLINICAL PRESENTATION AND DIAGNOSIS

Retinoblastoma is the most common pediatric malignant ocular tumor. Retinoblastoma presents most commonly as either leukocoria (white pupil), strabismus, or with signs of ocular inflammation. The inflammation from retinoblastoma often causes a red, painful eye that is photophobic. A hypopyon may be present as well as a ‘pseudohypopyon’, which actually represents a layering of the tumor cells in the anterior chamber.

Diagnosis is usually suspected with direct visualization of the tumor. Ocular ultrasound and/or computed tomography (CT) may be performed to demonstrate intraocular calcification.

MANAGEMENT/TREATMENT AND PROGNOSIS

Treatment for large tumors is most often enucleation. Multiple ‘eye-sparing’ techniques have recently gained favor. These include scleral plaque radiotherapy, phototherapy, cryotherapy, chemotherapy, and external beam radiation.11

Without treatment, most children die within 2 years. However, with modern therapies, prognosis is very good, with a cure rate of greater than 95%. Early diagnosis and treatment have the best outcomes. Children with retinoblastoma that has invaded into the optic nerve, choroid, sclera, orbit, or anterior chamber often require chemotherapy, and have a poorer prognosis.

Leukemia

CLINICAL PRESENTATION AND DIAGNOSIS

The most common ocular presentation of systemic leukemia is retinal hemorrhages on fundus examination. Leukemic infiltrates within the uvea may lead to pseudoanterior iritis, which can layer out in the anterior chamber forming a hypopyon (210). Choroidal involvement generally presents as serous retinal detachments and optic nerve involvement presents as papilledema.12

Definitive diagnosis is made with bone marrow biopsy and smear. Aqueous tap may also be performed for cytology.

MANAGEMENT/TREATMENT AND PROGNOSIS

Treatment of systemic leukemia is managed by a hematologist/oncologist and is outside the scope of this book. Optic nerve infiltration is an ophthalmic emergency and requires radiation therapy to prevent permanent vision loss. With early radiation therapy, vision can often be saved in optic nerve-related disease.

210

Ophthalmologists frequently evaluate infants and children with visual loss from diseases of the optic nerve. It is essential to diagnose the cause of the optic neuropathy accurately, not only for treatment and prognosis regarding vision, but also to detect associated neurologic and systemic disorders.1

Several clinical principles apply to children with optic nerve dysfunction. Children with bilateral optic neuropathy acquired prior to 2 years of age often present with nystagmus. Children with unilateral optic neuropathy often present with strabismus due to loss of vision (sensory strabismus). Color vision is typically normal in children with visual loss from a congenitally anomalous optic nerve. This is in contrast to the dyschromatopsia that occurs in children with acquired optic neuropathies.1

It should be remembered that a structural ocular abnormality in infants and children may lead to superimposed amblyopia.2 Therefore, a trial of occlusion therapy is often warranted in children with unilateral optic neuropathies and decreased vision. Vision may improve with occlusion therapy even among children who have a relative afferent pupillary defect.1

DEFINITION/OVERVIEW

Optic nerve hypoplasia is a developmental anomaly in which there is a subnormal number of axons within the affected nerve, although the mesodermal elements and glial supporting tissue of the nerve are normal.

ETIOLOGY

Certain prenatal pharmacological insults may be associated with the development of optic nerve hypoplasia. Drug associations include exposure to phenytoin, quinine, lyseric acid diethylamide, meperidine, diuretics, and corticosteroids. The presence of maternal diabetes mellitus has also been implicated in some cases.

CLINICAL PRESENTATION

Children present with unilateral or bilateral reduction in vision. Children with a significant impairment of vision in both eyes will present early with nystagmus. Patients with unilateral optic nerve hypoplasia often present after failing a vision screening test or with strabismus.

The hypoplastic optic disc appears abnormally small and is often gray or pale in color (211, 212). The disc may be surrounded by a yellowish peripapillary halo bordered by a dark pigment ring (double ring sign) (213).3 Associated retinal vascular tortuosity may occur. Histologically, optic nerve hypoplasia is characterized by a subnormal number of optic nerve axons with normal mesodermal elements and glial supporting tissue.3 Magnetic resonance imaging (MRI) will often show a small optic nerve and chiasm in children with optic nerve hypoplasia.4

Visual acuity may range from 20/20 to no light perception and does not necessarily correlate with the overall size of the optic disc. Visual fields often have localized defects as well as general constriction.5

Optic nerve hypoplasia is associated with multiple central nervous system (CNS) malformations. Septo-optic dysplasia (de Morsier’s syndrome) refers to the combination of small anterior visual pathways, absence of the septum pellucidum, and agenesis or thinning of the corpus callosum.6 Cerebral hemispheric migration anomalies (schizencephaly, cortical heterotopias) or intrauterine or perinatal

hemispheric injury (periventricular leukomalacia, encephalomalacia) occur in 45% of patients with optic nerve hypoplasia. These abnormalities are highly predictive of neurodevelopmental deficits.7

DIAGNOSIS

MRI demonstrates neurohypophyseal abnormalities in approximately 15% of children with optic nerve hypoplasia.1,7 In normal children, MRI delineates the pituitary infundibulum, anterior pituitary gland, and the posterior pituitary gland, which appears as a ‘bright spot’ located in the sella (214). In children with optic nerve hypoplasia, absence of the infundibulum, or posterior pituitary ectopia may occur (215). Posterior pituitary ectopia denotes the abnormal location of the posterior pituitary in the hypothalamus. These pituitary abnormalities are associated with endocrinologic dysfunction.7–9 Some children have an absent pituitary infundibulum and no ‘bright spot’ (216). These children are at high risk for anterior and posterior pituitary dysfunction with diabetes insipidus.9

MANAGEMENT/TREATMENT

There is no treatment available to improve the vision that is decreased due to the hypoplastic optic nerve(s). If there is a possibility of superimposed amblyopia, treatment should be initiated. Low-vision services are warranted for those patients with significantly reduced vision.

The detection of endocrinologic dysfunction is an essential component of the evaluation of children with optic nerve hypoplasia. Growth hormone insufficiency is the most common endocrinologic abnormality associated with optic nerve hypoplasia.10,11 However, hypothyroidism, hypocortisolism, panhypopituitarism, diabetes

insipidus, and hyperprolactinemia may also occur.3,12–14 Children with undiagnosed endo-

crinologic deficiency are at risk for impaired growth, hypoglycemia, seizures, and death.15 Early pituitary hormone replacement may prevent or ameliorate these complications. Therefore, parents should be questioned regarding the presence of protracted neonatal jaundice (associated with hypothyroidism) and previous episodes of neonatal hypoglycemia (associated with hypocortisolism). As noted above, MRI is helpful for the detection of endocrinologic dysfunction in children with optic

nerve hypoplasia.8 Children with either a history suggestive of pituitary dysfunction or neurohypophyseal abnormalities on cranial MRI (such as absence of the infundibulum or posterior pituitary ectopia), should undergo diagnostic endocrinologic evaluation.

SPECIAL FORMS OF OPTIC NERVE HYPOPLASIA

Children with periventricular leukomalacia often have a special form of optic nerve hypoplasia characterized by a large cup and a

thin, narrow retinal rim within a normal sized optic disc.16,17 This appearance has been

attributed to bilateral injury to the optic radiations with retrograde trans-synaptic degeneration of retinogeniculate axons after the scleral canals have developed to a normal diameter.

Superior segmental optic nerve hypoplasia with an inferior visual field defect occurs in

some children of insulin-dependent diabetic mothers (217).18,19

214

214 Cranial magnetic resonance imaging:T1 weighted,sagittal view of a patient with optic nerve hypoplasia and normal endocrinologic function.Note presence of the infundibulum and the bright spot denoting the posterior pituitary located in the sella.(From Phillips PH,Spear C, Brodsky MC (2001).Magnetic resonance diagnosis of congenital hypopituitarism in children with optic nerve hypoplasia.J AAPOS 5(5):275–280,with permission.)

215

215 Cranial magnetic resonance imaging:T1 weighted,sagittal view of a patient with optic nerve hypoplasia and anterior pituitary dysfunction.There is absence of the infundibulum and posterior pituitary ectopia. (From Phillips PH,Spear C,Brodsky MC (2001). Magnetic resonance diagnosis of congenital hypopituitarism in children with optic nerve hypoplasia.J AAPOS 5(5):275–280,with permission.)

216 Cranial magnetic resonance imaging:sagittal view of a patient with optic nerve hypoplasia and panhypopituitarism.The patient has diabetes insipidus.There is absence of the infundibulum and no detectable posterior pituitary gland (absence of the posterior pituitary bright spot). (From Phillips PH,Spear C, Brodsky MC (2001). Magnetic resonance diagnosis of congenital hypopituitarism in children with optic nerve hypoplasia.J AAPOS 5(5):275–280,with permission.)

217 Fundus photograph,right eye,of a 14-year- old girl who presented with a right inferior visual field deficit.Her mother was aType I diabetic.

This figure denotes superior segmental optic nerve hypoplasia.