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

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TABLE 5-1. Varieties of Retinitis Pigmentosa and Associated

Disorders.

Retinitis pigmentosa (RP)

Clinical features

Workup

Treatment

Hereditary subtypes of typical RP

Autosomal dominant

Autosomal recessive

X-linked

Leber’s congenital amaurosis

RP and systemic diseases

Usher syndrome

Alstrom disease

Bardet–Biedl syndrome

Retinal renal syndromes

Ceroid lipofuscinoses

Mitochondrial diseases

Other photoreceptor disorders

Congenital stationary night blindness

Cone dystrophies

Dyschromatopsias

Other RP-like retinal disorders

Unilateral pigmentary retinopathy

X-linked juvenile retinoschisis

Goldmann–Favre syndrome

Gyrate atrophy

Choroideremia

stationary night blindness, cone dystrophies, and congenital dyschromatopsias.

RETINITIS PIGMENTOSA (PROGRESSIVE ROD/CONE DYSTROPHY)

Clinical descriptions of night blindness consistent with the diagnosis of retinitis pigmentosa (RP) were made as early as 1744 by Ovelgun. Donders first used the phrase “retinitis pigmentosa” in 1855. Karpe is credited with developing clinical electroretinography (ERG) in 1945. He detected abnormally low ERGs in patients with RP and noted that these abnormalities could precede the onset of ophthalmoscopically visible changes. Gouras and Carr subsequently identified preferential rod photoreceptor dysfunction in patients with early autosomal domi-

nant retinitis pigmentosa.57 In 1989, McWilliam et al.98 reported linkage of the disease phenotype in a large family with autosomal dominant RP (ADRP) to a genetic marker on the long arm of chromosome three. The proximity of this marker to the rhodopsin gene led Dryja and his co-workers34–39 to examine the rhodopsin gene in patients with ADRP, and in 1990 they identified the first rhodopsin mutations in such patients. In 1991, two groups identified ADRP-causing mutations in the peripherin/ RDS gene.40,74 Subsequently, retinitis pigmentosa has been proven to be a very genetically heterogeneous group of disorders.20,68,71,135 Of interest, genotype–phenotype correlations are rarely strong. In fact, for the inherited retinopathies the rule has been that disorders that look clinically similar may have different genetic causes, whereas those with identical gene defects may present with very different clinical findings. Because of this, arguments can be made for discarding the existing clinically based nomenclature in favor of one that describes the genetic subtype of the disorder. In reality, however, most diagnoses still must be made clinically at this writing.

Clinical Features

The earliest symptom of RP and related disorders is often night blindness. Young children may not be capable of articulating this, and some patients may not give a history of subjective night blindness even when objective difficulty with dark adaptation can be documented. Parents should be asked whether their child clings to them or guides himself or herself along walls or furniture in dimly lit rooms or movie theaters. A child’s activity in the exam room can also be evaluated after dimming the lights. Older children and adults may describe themselves as clumsy or admit to difficulty seeing the stars at night or finding their seat in a dark theater. Often children with RP are referred because of decreased visual acuity or the discovery of abnormal fundus pigmentation on routine ocular examination. Some children come to an ophthalmologist because of a positive family history without any symptoms themselves. Fundus findings include arteriolar narrowing, waxy pallor of the disc, cystoid macular edema and bone spicule-like pigment changes (Figs. 5-1, 5-2, 5-3). Vitreous cells and posterior subcapsular cataracts are also commonly observed.

Pigmentary changes in the fundus are variable and may even be absent (retinitis pigmentosa sine pigmento), making

FIGURE 5-2A,B. Fluorescein angiogram of a patient with Usher syndrome. (A) Early phase of the angiogram. Subtle abnormalities of the foveal avascular zone are visible. (B) Late phase of the angiogram. Pronounced cystoid macular edema and deep retinal pigment epithelial leakage are evident.

symptoms and family history especially important in the decision to proceed with further evaluation. White dots may also be observed deep in the retina; when marked, this appearance is known as retinitis punctata albescens (RPA). Fundus albipunctatus (FAP) has similar white dots, but is associated with a

FIGURE 5-3A,B. Fundus photographs of a patient with rhodopsin-asso- ciated retinitis pigmentosa (Val-87-Asp). The retinal degeneration is more pronounced in the inferior quadrants than the superior quadrants and involves the macula as well. The visual fields from this patient are shown in Figure 5-5.

stationary night blindness, not progressive RP. Historically, the uniqueness of retinitis pigmentosa sine pigmento and retinitis punctata albescens has been argued, because both have been observed in affected patients from ADRP and ARRP pedigrees in which other family members demonstrate bone spicules and

typical fundus changes characteristic of retinitis pigmentosa. RP sine pigmento is believed by most investigators to be an early stage of RP before the bone spicule-type of hyperpigmentation and atrophy are manifest.116 RPA has been seen in various subtypes of early stages of RP.100 One family with an RPA appearance was found to have a heterozygous mutation of the RDS/peripherin gene.75 A consanguineous pedigree from Saudi Arabia with ARRP with a RPA phenotype was found to be caused by homozygous mutations in the RLBP1 gene and was slowly progressive.79

Workup

A standard clinical evaluation for a patient suspected to have an inherited retinal dystrophy includes a history and physical examination directed toward the signs and symptoms of rod and cone photoreceptor dysfunction. In addition to refraction, retinal biomicroscopy, and indirect ophthalmoscopy, we usually include three laboratory tests in the workup as well: visual field evaluation, dark adaptometry, and electroretinography. The purpose of these three tests is to determine the presence or absence of retinal disease, to confirm and refine the diagnosis, and to establish a baseline level of visual function. In at least one patient per family, DNA screening for known retinal dystrophy mutations may be offered.

Visual field loss is progressive in the rod and cone dystrophies and may demonstrate variability as the disease progresses. Early in the course of retinitis pigmentosa, paracentral scotomas and, later, a complete ring scotoma may be seen (Fig. 5-4). Some patients with rhodopsin-associated retinitis pigmentosa show a preferential superior visual field loss65,133 (Fig. 5-5). Late in the course of retinitis pigmentosa, the ring scotomas break out into the periphery and there is progressive constriction of the peripheral isopters. Typically, only a small central island remains, occasionally accompanied by another temporal island in the periphery (Fig. 5-6). Legal blindness in many states is defined by less than 20° of a central island to a III4e isopter. RP patients may be legally blind on the basis of constricted visual fields even though they have relatively good central vision. Visual field loss is generally symmetrical between both eyes, and marked asymmetry may suggest a nonhereditary basis for poor vision.

Dark adaptometry measures the patient’s threshold for detecting a test spot of light as they progressively adapt to darkness.