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

FIGURE 13-8. Searching for transillumination defects in a young child using the penlight technique. In this photograph, the red reflex from the camera flash illuminates both eyes. In clinical use, the flashlight held to the lids in a darkened room reveals iris transillumination defects beautifully, a test that is much easier to perform than a slit lamp examination in most infants. (Courtesy of Dr. G.F. Judisch)

are pink. In the various incomplete forms, and in all ocular albinism patients, the signs may be far more subtle. Pigmentation may appear normal, but may be less than expected given the patient’s racial and ethnic background and the parents’ pigmentation. In such patients, a careful search for iris transillumination defects and foveal abnormalities should be performed in the proband and family members.

Infants with albinism often have delayed visual responses suggesting the diagnosis of Leber’s congenital amaurosis. Vision often improves with time to approximately 20/200 with even better vision at near. The optic nerves may appear gray or indistinct (Fig. 13-9), and macular hypoplasia may be so profound that retinal vessels course over the area that should include the macula.78 A history of easy bruising or frequent infection should be sought to rule out the potentially life-threatening syndromes of Hermansky–Pudlak and Chediak–Higashi. The fundus appears blonde in all forms of albinism; however, small pigmented RPE clumps or diffuse moderate pigmentation may be seen in tyrosinase-positive incomplete OCA patients. The other disorder in which foveal hypoplasia is prominent is aniridia (Fig. 13-10). Affected infants present with poor vision, nystagmus, and hypoplasia of the iris. Most patients have some rudimentary iris tissue and may therefore appear to have widely dilated amaurotic pupils, leading to an erroneous diagnosis. The macular

reflex is blunted but the fundus pigmentation is normal for that individual. It is usually possible to see the edge of the lens, which may be easier to do with a 20 diopter (D) lens and an indirect ophthalmoscope than a slit lamp in a very young child. The diagnosis of aniridia is an important one because sporadic cases are associated with Wilm’s tumor. Such children should have close follow-up by a pediatrician throughout childhood. The hereditary forms may be autosomal dominant or recessive. In some dominant pedigrees of aniridia, foveal hypoplasia is not present, there is no nystagmus, and vision is good.16 Glaucoma often may develop in patients with aniridia. Congenital, developmental, and angle-closure glaucoma have also been reported in association with albinism.9,17,43

Retinal Detachment

Retinal detachment in infants and children is extremely rare, and this finding should lead one to suspect a specific disease, syndrome, or trauma. Nonaccidental trauma should always be considered because in these cases the child’s life, as well as vision, may be at stake.

Several broad categories should be considered when a newborn or infant presents with a retinal detachment. The first is the presence of a tumor in the eye, which should be ruled out with ultrasound or CT scan. Once this potentially lifethreatening diagnosis has been excluded, other causes of congenital or infantile detached retina should be considered, including Stickler syndrome, retinopathy of prematurity, retinal dysplasia, and Norrie disease (Fig. 13-11). The latter may be confirmed by molecular genetic techniques and is caused by mutations of the Norrie disease gene on the X chromosome.92 Defects in this gene may also cause later onset retinal detachment as part of familial exudative vitreoretinopathy (FEVR).11 Premature infants with mutations in the Norrie disease gene may be predisposed to more severe ROP and retinal detachment as well.70

FIGURE 13-11A,B. Sagittal (A) and axial (B) MRI of a child with Norrie disease. Note the blood density filling the globe and the detached retina anterior to it. MRI or CT may distinguish this disorder from retinoblastoma, but not from vitreous hemorrhage or persistent hyperplastic primary vitreous (PHPV). Retinal detachment in Norrie disease is usually, although not always, bilateral. (Courtesy of Dr. I. Maumenee)

Persistent hyperplastic primary vitreous (PHPV), also called persistent fetal vasculature (PFV), may also present with a retinal detachment at birth; however, the associated microphthalmos and cataract often simplify the diagnosis. Bilateral PHPV may be a sign of a genetic syndrome. A complete systemic and genetic workup should be performed in these cases. In infants who are born with attached retinas that subsequently detach, a likely diagnosis is cicatricial retinopathy of prematurity. There is evidence that retinal degeneration occurs very rapidly following detachment in these immature eyes.38 Incontinentia pigmenti may also predispose to early-onset retinal detachment. If retinal detachments occur in later infancy or childhood, underlying exudative, inflammatory, or tractional causes should be sought. The retinal detachments seen with Stickler’s syndrome, spondyloepiphyseal dysplasia congenita, X-linked juvenile retinoschisis, optic nerve pits, and Ehlers– Danlos VI usually occur after infancy. In Ehlers–Danlos VI, there may be extreme fragility of the globe resulting in rupture from relatively minor injury. Safety glasses should be prescribed for these children. Some, although not all, of the latter patients have a measurable deficiency of lysyl dehydrogenase.34 Pyridinium cross-link abnormalities in urine may help make the diagnosis of Ehlers–Danlos VI.

Angioid Streaks

Angioid streaks are seen ophthalmoscopically as subretinal lines of variable width, usually radiating out from the disc (Fig. 13-12), which represent breaks in Bruch’s membrane with atrophy of the overlying RPE and eventually of the underlying choriocapillaris as well. The color of the streaks may be red or gray (recent) or yellowish (atrophic). About half the patients with angioid streaks have an underlying systemic cause.13,73 The associated disorders (Table 13-1) are syndromes in which elastic tissue is abnormally fragile because of either an increased affinity for calcium or deposition of iron. The breaks in Bruch’s membrane may be secondary to mechanical forces acting on this relatively inelastic structure.46 Angioid streaks usually develop in the second decade of life and are associated with macular subretinal neovascular membranes, macular degeneration, and visual loss in more than 50% of eyes, often at a young age.47

to irregular degeneration of the RPE with adjacent pigment migration and clumping.93 However, the vision and electrooculogram (EOG) are usually normal, and the electroretinogram (ERG) is recordable but may be reduced.39 In later life (after the age of 9 years in all reported patients), subretinal neovascular membranes may form. Some of these membranes resolve without disciform scarring but others reduce vision.75 Other ocular findings may include cataract, microphthalmos, and glaucoma. Hearing loss is common, and endocrine abnormalities also develop in some patients later in life, making the appropriate diagnosis of more than academic interest.69 Infants born with congenital rubella can shed live virus and are therefore infectious. Interestingly, they may not retain immunity from their congenital infection and are therefore susceptible to reinfection at a later time. For the same reason, negative rubella titers in a child older than 3 or 4 years do not rule out congenital infection. Although vaccination programs have all but eradicated epidemics of rubella in the United States, 10% to 20% of adults in their childbearing years remain seronegative,76 and cases of congenital rubella continue to be reported in the United States and around the world.

Another congenital infection causing this fundus picture is syphilis. The incidence of this disease is on the rise in the United States. Babies often have rhinitis causing the “sniffles” shortly after birth. Retinitis, uveitis, interstitial keratitis, and abnormal teeth develop later. If congenital syphilis is diagnosed at any age, systemic antibiotics may be warranted. Even if treated, congenital syphilis may lead to recurrent uveitis, arthritis, progressive hearing loss, and interstitial keratitis mediated by autoimmune effects. Any child with positive syphilis serology should be evaluated for other sexually transmitted diseases such as human immunodeficiency virus (HIV), gonorrhea, and chlamydia.

Alstrom syndrome may resemble congenital rubella with deafness, pigmentary retinopathy, and diabetes mellitis. Although the fundus may have a salt-and-pepper appearance, a bull’s-eye or other maculopathy is more typical. The histopathology is very different from congenital rubella, with an absence of rods and cones.68 The ERG may initially show a cone defect but usually becomes nonrecordable over time. Mitochondrial myopathy may also be associated with salt-and-pepper retinopathy. In a series of 61 patients with mitochondrial myopathy, 36% had retinal pigmentary changes. Of these, 82% were described as “salt and pepper,” usually with good vision.53

Bull’s-Eye Maculopathy

The neuronal ceroid lipofuscinoses (NCL) are a group of autosomal recessive disorders characterized by progressive neurological deterioration, seizures, and pigmentary retinopathy. Three of the four types exhibit retinopathy. The infantile form (Haltia–Santavuori syndrome, onset between 8 and 18 months of age) and the late infantile form (Jansky–Bielschowsky syndrome, onset between 2 and 4 years of age) usually present with neurological deterioration before vision loss occurs. In the juvenile form (Batten syndrome), the onset is between 4 and 8 years of age and the visual disturbance usually precedes neurological symptoms; this form is most likely to be diagnosed by an ophthalmologist. The earliest ophthalmoscopic finding is usually a decreased foveal reflex or bull’s-eye maculopathy (similar to that shown in Figs. 13-14A,B). In contrast to NCL, olivopontocerebellar atrophy type III also called SCA 6 (spinocerebellar atrophy 6) is an autosomal dominant disorder. The age of presentation is extremely variable, and patients with a younger age of onset are usually more severely affected. Visual problems may be the first symptoms, especially in older children or young adults. A bull’s-eye or atrophic maculopathy may be present and with time may become diffuse. Subtle cerebellar signs should be sought because these may be present even in patients who have not yet complained about neurological problems. Older family members should be examined for maculopathy which may appear isolated.82

Hallervordan–Spatz syndrome is an autosomal recessive disorder with rapidly progressive neurological and retinal deterioration and death. In some patients, early symptoms may be subtle and psychological disorders are initially suspected. The retinopathy is typically of a flecked type with a bull’s-eye maculopathy.14 Stargardt’s disease is usually an autosomal recessive disorder although autosomal dominant pedigrees have been described (see Chapter 4). The usual presentation is with gradual bilateral visual loss in the first two decades of life. The fundus picture includes a beaten bronze or bull’s-eye macular appearance with or without peripheral flecks. Stargardt’s and fundus flavimaculatus are probably the same disorder because both can occur in the same pedigree and have been associated with the same gene in some pedigrees. The visual disturbance may precede the pigmentary changes, leading to an erroneous diagnosis of hysterical blindness.25 The Bardet–Biedl syndrome is an