Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Retinal Disease_Wright, Spiegel, Thompson_2006

autosomal recessive disorder that has features which are evident at birth. However, diagnosis is frequently delayed until later in life. Polydactyly, obesity, hypogenitalism, and at times mild mental retardation accompany a pigmentary retinopathy that is usually apparent in the early school years along with markedly decreased vision. A bull’s-eye maculopathy is often seen, although in some patients pigmentary changes may be subtle. The ERG may initially show rod dysfunction but can progress to nonrecordable. The Lawrence–Moon syndrome is similar to Bardet-Biedl, but there is no polydactyly and spastic paraplegia may be present.65

Some medications and toxins may cause a retinopathy that often begins as, or includes, a bull’s-eye maculopathy. The iron chelator desferoxamine is commonly used in children who are transfusion dependent as a result of sickle cell disease or thallasemia. A progressive, severe retinopathy with gradual pigmenatary changes of the macula may result, with concomitant ERG changes. Rapid discontinuation of the medication may restore vision. It may be prudent to follow children on chronic desferoxamine therapy with serial ERGs. This drug can also cause optic neuropathy. Chloroquine can cause maculopathy as well.

Congenital Retinal Disease

The ophthalmologist is frequently called upon to examine the eyes of a newborn suspected to have an infection contracted in utero. The eye examination can help make a rapid diagnosis in some cases, allowing appropriate treatment to be started. Some infections can cross the blood–placenta barrier, whereas others are contracted when there is premature rupture of membranes or during the baby’s passage through the birth canal. All of the TORCH infections (toxoplasmosis, rubella, cytomegalovirus, and herpes), as well as HIV, can cross the placenta, and antibody titers can be drawn at birth. Because IgG crosses the placenta, and therefore may be of maternal origin, IgM titers should be examined specifically. Titers drawn after the first few months of life should be interpreted with caution because exposure may have occurred postnatally. Rubella virus interferes with organogenesis. Affected children are small, and the organs actually have fewer cells than normal. For this reason, children affected later in gestation, after most of the organs have formed, have few or no defects. Live virus may persist for years in the various

prenatally and postnatally if congenital infection has occurred. Combination antibiotic treatment for congenital toxoplasmosis must be continued for at least 1 full year and should be combined with systemic steroids and close monitoring if active retinal lesions are present.48 Similarly, babies born with congenital herpes may require antiviral medication in the neonatal period.

In all these disorders the chorioretinitis appears similar, and the importance of ophthalmoscopy is not to differentiate between these infections but to identify an abnormality and stimulate an appropriate workup including CT scan of the head and serologies. It is not yet known whether congenital HIV can cause a typical chorioretinitis. Cotton wool spots may be present. Opportunistic infections must be ruled out in these infants, and whenever one sexually transmitted disease is present, the possibility of others, including chlamydia, must be excluded. Cytomegalovirus (CMV) retinitis in children may not present with the acute hemorrhagic picture seen in adults.45 Parents of infants with quiescent toxoplasmosis lesions should be informed about the possibility of reactivation. Pregnant women should be advised to avoid undercooked meat and contact with cat feces, which may harbor the toxoplasmosis organisms. Lymphocytic choriomeningitis virus (LCMV) can also cross the placenta. This virus is carried by rodents such as mice, rats, and hamsters. A pigmentary retinopathy with coloboma-like lesions may result. Titers for LCMV should be drawn in suspected congenital infection cases.51

Geographic Pigmentary Disturbances

Several disorders occurring during childhood may present with progressive geographic pigmentary changes in the fundus. Pathological myopia (Fig. 13-16) may cause confluent areas of chorioretinal degeneration in the posterior pole. There may be excavation of the region, and the sclera can be seen. Isolated pathological myopia usually appears to be autosomal recessive or sporadic. Several connective tissue disorders with systemic features have pathological myopia as an associated finding, however, and a complete physical examination should be performed in any child with pathological myopia. Gyrate atrophy (Fig. 13-17) causes confluent areas of chorioretinal atrophy in the periphery that progress toward the posterior pole over time. Choroidal vessels and some pigmentation are often visible within the atrophic patches. This disorder is also autosomal

recessive and is associated with high myopia in childhood. Night blindness is also a feature. The diagnosis can be made by detecting elevated plasma ornithine levels. Dietary changes may halt progression. The cause is a mutation of the ornithine aminotransferase gene, leading to hyperornithinemia. Myopia, early-onset cataracts, and abnormal ERG are also found.57 Choroideremia is X-linked recessive, and affected patients are therefore almost always male. Night blindness is present, but high myopia is not usually seen. The chorioretinal atrophy is seen first in the midperiphery and also has scalloped edges. It is caused by mutations in the RAB27A gene.80

Retinal Causes of Leukocoria

Leukocoria in an infant or young child may be secondary to corneal or lens pathology. Once these factors are excluded, a retinal source is likely. The first step is always to rule out retinoblastoma, because this is a potentially fatal condition that has a fairly good prognosis with treatment (see Chapter 9). Fundus examination, ultrasound, and CT scan all have a role in the evaluation of these patients. The child may need to be sedated to obtain an optimal examination. Many other disorders with various etiologies can cause the normal red reflex to appear whitish or yellow (Table 13-1). In general, any disorder that destroys, detaches, or changes the normal color of the retina in an area likely to be in line with the pupil (i.e., the posterior pole) can cause leukocoria.

SYSTEMIC DISORDERS ASSOCIATED WITH RETINAL ABNORMALITIES

Ichthyosis and Other Dermatological Disorders

In a child presenting with retinal disease, the first step in a general examination should be an evaluation of the skin. Ichthyosis is abnormal scaling, dryness, and tightness of the skin. Isolated ichthyosis is commonly associated with anterior segment complications, but ichthyosis in association with pigmentary retinopathy should suggest the diagnoses of Refsum disease60 or

Sjogren–Larsson syndrome74 (see Table 13-2). Darier’s disease is an autosomal dominant disorder characterized by scaling, papules, and dystrophic nails. Typical retinitis pigmentosa has been

reported in association with this disease.31 Other skin findings that should alert the ophthalmologist to the presence of a systemic syndrome are whorls of brown pigment, usually on the trunk, that were preceded in infancy by blister-like lesions (incontinentia pigmenti), atrophic changes (Flynn-Aird syndrome),18 skin photosensitivity (Cockayne syndrome and Allagille syndrome), or areas of hypopigmentation (vitiligo and Vogt–Koyanagi–Harada). Petechial lesions may be seen in Fabry’s disease (Fig. 13-18). A “plucked chicken” appearance (Fig. 13-19A) is characteristic of pseudoxanthoma elasticum. The presence of “peau d’orange” fundus changes (Fig. 13-19B) is essentially pathognomonic of this disorder,49 unlike the less specific finding of angioid streaks (see Fig. 13-12).

Linear atrophic scarlike lesions on the face, neck, and upper body may be associated with retinal colobomas or Peter’s anomaly in Goltz syndrome and microphthalmia with linear skin defects (MLS), respectively. Both are X-linked dominant.94

Deafness

A significant number of deaf children have associated retinopathy. Deaf children are often referred for ophthalmologic evaluation both to ensure optimal function of their remaining sensory input and to rule out the presence of a syndrome. These syndromes can be divided into those that typically present with deafness and those which present first with visual problems. In the former group, the most common disorder is Usher syndrome, types I and II. Patients with type I Usher syndrome are born with profound deafness and vestibular abnormalities. Retinopathy, night blindness, and ERG changes usually occur in the first decade of life. In type II, abnormal hearing is present at birth, but is less severe, and vestibular function is intact. Retinopathy does not begin until the teens. There are many subsets of these two types, and at least six different genetic loci have been identified.8 Usher syndrome is autosomal recessive, and there is also a lateronset form (type III) with progressive hearing loss and retinopathy in adulthood. Infants born with congenital rubella syndrome often have hearing loss, in association with a salt-and-pepper retinopathy and, at times, cataracts.

Alport syndrome is a relatively common disorder. Hearing loss, which may be mild initially, is usually present within the first decade, along with renal disease. Approximately 30% of patients develop ocular involvement, with males predominat-

TABLE 13-2. Diseases with Systemic Signs Associated with Retinal Abnormalities.

1.Ichthyosis and other dermatological disorders

a.Sjogren–Larsson syndrome

b.Refsum’s disease

c.Incontinentia pigmenti

d.Pseudoxanthoma elasticum

e.Darier’s disease

f.Flynn–Aird syndrome

g.Allagille syndrome

h.Cockayne syndrome

i.Vogt–Koyanagi–Harada

j.Vitiligo

k.Goltz syndrome/MLS

2.Deafness

a.Usher’s syndrome

b.Alstrom syndrome

c.Refsum disease

d.Alport syndrome

e.Congenital rubella

f.Cockayne syndrome

g.Peroxisomal disorders

h.Mucopolysaccharidoses

i.Kearns–Sayre syndrome

j.Osteopetrosis

k.Norrie disease

l.Flynn–Aird syndrome

m.Cogan’s syndrome

n.Stickler’s syndrome

o.Spondyloepiphyseal dysplasia congenita

3.Polydactyly

a.Bardet–Biedl syndrome

b.Jeune’s syndrome

c.Trisomy 13

4.Short stature/skeletal anomalies/facial dysmorphism

a.Bardet–Biedl syndrome

b.Cockayne syndrome

c.Jeune’s syndrome

d.Osteopetrosis

e.Spondyloepiphyseal dysplasia congenita

f.Mucopolysaccharidosis IH, IS, II, III

g.Stickler’s syndrome

h.Infantile phytanic acid storage disease (infantile refsum)

i.Allagille syndrome

j.Chorioretinopathy and pituitary dysfunction

5.Renal disease

a.Senior–Loken syndrome

b.Bardet–Biedl syndrome

c.Alport’s syndrome

d.Idiopathic infantile hypercalcuria

e.Renal dialysis

f.Oxalosis

TABLE 13-2. (continued)

g.Cystinosis

h.Renal-coloboma syndrome

i.Alstrom syndrome

6.Hepatic disease

a.Allagille syndrome

b.Zellweger’s syndrome

7.Neurological/neuromuscular disorders

a.Neuronal ceroid lipofuscinosis

b.Olivopontocerebellar atrophy type III (SCA 6)

c.Kearns–Sayre syndrome

d.Myotonic dystrophy

e.Hallervorden–Spatz disease

f.Joubert syndrome

g.Mucolipidoses

h.Zellweger’s syndrome

i.Neonatal adrenoleukodystrophy

j.Refsum’s disease

k.Infantile phytanic acid storage disease

l.Flynn–Aird syndrome

m.Abetalipoproteinemia

8.Obesity

a.Bardet–Biedl syndrome

b.Alstrom syndrome

ing.32 The most common ocular finding is anterior lenticonus, which is not present at birth but develops later in childhood or adolescence. Retinal changes, which may appear as RPE mottling or whitish dots, are also a later finding.7,64 Alport syndrome is genetically heterogeneous, with approximately 80% of cases X-linked recessive and most of the remainder autosomal recessive; it is caused by mutations in various genes coding for basement membrane type IV collagen.3,36 Some patients develop leiomyomas of the esophagus, tracheobronchial tree, and genitalia (in females).

The presenting sign in Flynn–Aird syndrome is usually hearing loss, with retinopathy and neurological changes occurring later. This rare disorder is autosomal dominant, but symptoms often do not appear until early adulthood.18 In the congenital rubella syndrome, deafness is usually present at birth and the typical salt-and-pepper retinopathy, which is either congenital or develops within the first year, may help to make the diagnosis. Rarely, deafness may not develop until later in childhood.69 In contrast to the preceding disorders, children with Norrie disease or Alstrom syndrome present with a visual problem and only later develop hearing loss. In several other dis-

FIGURE 13-18A,B. (A) Characteristic skin lesions in a young man with Fabry’s disease. (B) Another patient with Fabry’s disease demonstrates characteristic spoke-like lens opacities on retroillumination. Corneal changes may also occur and have a whorled pattern.

orders, the retinal disease and deafness develop at approximately the same age. Thus, the ophthalmologist examining a child in whom hearing loss has been recently diagnosed must suspect these disorders. Similarly, children with newly diagnosed retinal disease suggestive of one of these syndromes should be