Familial dysautonomia

Familial dysautonomia (Riley-Day syndrome), a complex autosomal recessive condition, occurs largely in children of Eastern European Jewish (Ashkenazi) descent. It is characterized by autonomic dysfunction, relative insensitivity to pain, temperature instability, and absence of the fungiform papillae of the tongue. Exposure keratitis and corneal ulcers with secondary opacification are frequent problems because of abnormal lacrimation and decreased corneal sensitivity. Failure to respond with a wheal and flare to intradermal injection of 1:1000 histamine solution is characteristic of this condition. Treatment includes artificial tears and tarsorrhaphy. Most cases of familial dysautonomia are caused by a mutation in the IKBKAP gene.

Waardenburg syndrome

Waardenburg syndrome is a rare neurocristopathy characterized by Hirschsprung disease, deafness, and depigmentation of hair (a white forelock), skin, and iris.

Tumors of the Cornea, Iris, and Anterior Segment

Cornea

Tumors of the cornea are extremely rare in children, but squamous cell carcinomas have been reported in cases of xeroderma pigmentosum.

Iris

Nodules

Lisch nodules Lisch nodules occur in patients with neurofibromatosis (see Chapter 28).

Juvenile xanthogranuloma Juvenile xanthogranuloma is a nonneoplastic histiocytic proliferation that develops in infants younger than 2 years. It is characterized by the presence of Touton giant cells. Skin involvement—consisting of 1 or more small, round, orange or tan papules—is typically but not always present. Iris lesions are relatively rare and virtually always unilateral. The fleshy yellowbrown masses may be small and localized or may diffusely infiltrate the entire iris, resulting in heterochromia. Spontaneous bleeding with hyphema is a characteristic clinical presentation. Secondary glaucoma may cause acute pain, photophobia, and vision loss. Those at greatest risk for ocular involvement are children with multiple skin lesions.

Juvenile xanthogranuloma is a self-limited condition that usually regresses spontaneously by age 5 years, but to avoid complications, treatment is indicated for ocular involvement. Topical corticosteroids and pharmacologic agents to lower intraocular pressure, given as necessary, are generally sufficient to control the problem. Surgical excision or radiation should be considered if intractable glaucoma is present.

Iris mammillations Iris mammillations may be unilateral or bilateral. They appear as numerous tiny, diffuse, pigmented nodules on the surface of the iris (Fig 20-15). They are more common in darkly pigmented eyes and are usually the same color as the iris. These nodules may be bilateral, autosomal dominant, and isolated, or they may be associated with oculodermal melanocytosis or phakomatosis pigmentovascularis type IIb (nevus flammeus with persistent, aberrant mongolian spots). Iris mammillations have also been reported in cases of ciliary body tumor and choroidal melanoma. They must be differentiated from Lisch nodules; mammillations are usually dark brown, smooth, uniformly distributed, and equal in size or slightly larger near the pupil. The incidence of iris

mammillations is higher among patients with neurofibromatosis 1.

Figure 20-15 Iris mammillations. Nodules are diffuse and are the same color as the iris (Lisch nodules, by contrast, are lighter or darker than the surrounding iris). (Courtesy of Arlene Drack, MD.)

Brushfield spots Focal areas of iris stromal hyperplasia surrounded by relative hypoplasia occur in up to 90% of patients with Down syndrome; in such patients, these areas are known as Brushfield spots. They are hypopigmented. Similar lesions, known as Wolfflin nodules, occur in up to 24% of healthy individuals. Neither condition is visually significant.

Cysts

Primary iris cysts These cysts may originate from the iris pigment epithelium or the iris stroma.

CYSTS OF IRIS PIGMENT EPITHELIUM Spontaneous cysts of the iris pigment epithelium result from a separation of the 2 layers of epithelium anywhere between the pupil and ciliary body (Fig 20-16). These cysts tend to be stable and rarely cause ocular complications. They are usually not diagnosed until the teenaged years.

Figure 20-16 Cysts of the pigmented epithelium of the iris at the pupillary border (flocculi).

CENTRAL CYSTS Pigment epithelial cysts at the pupillary border are sometimes hereditary. They are usually diagnosed in infancy. They may enlarge slowly but generally remain asymptomatic and rarely require treatment. Rupture of these cysts can result in iris flocculi. Cholinesterase-inhibiting eyedrops such as echothiophate may produce similar pupillary cysts, especially in young phakic eyes. Discontinuation of the drug or concomitant administration of phenylephrine generally results in improvement.

CYSTS OF IRIS STROMA Primary iris stromal cysts are often diagnosed in infancy. They are most likely caused by sequestration of epithelium during embryologic development. The epithelium-lined stromal cysts usually contain goblet cells, and they may enlarge, causing obstruction of the visual axis, glaucoma, corneal decompensation, or iritis from cyst leakage. Numerous treatments have been described, including cyst aspiration and photocoagulation or photodisruption, but the sudden release of cystic contents may result in transient iritis and glaucoma. Because of these potential complications and frequent cyst recurrence, surgical excision may be the preferred treatment method. Iris stromal