assessing the content of the lesion (exudate has a low internal reflectivity), and the size and shape of the involved area. Computed tomography (CT) is useful to distinguish Coats’ from retinoblastoma, which usually demonstrates areas of calcification within the tumor.

The exclusion of other causes of retinal exudate and elevation including tumors, infections, inflammation, retinal holes, and traction is necessary prior to making the diagnosis of Coats’ disease.

MANAGEMENT/TREATMENT AND PROGNOSIS

Management of Coats’ disease in the early stages is aimed at closure of telangiectatic vessels and microaneurysms by photocoagulation laser therapy. Treatment may halt the progression of the exudation, but the lipid accumulation does not usually resolve with treatment. In some cases closure of anomalous vessels may increase the intravascular pressure within collateral vessels and thereby worsen other areas by increasing the rate of vascular leakage. Once there is retinal detachment, cryotherapy may be useful, or surgery such as vitrectomy may help reattach the retina. For cases of advanced Coats’ disease, damage to the retina is severe and there is little hope of restoring useful vision. Glaucoma may develop, and the eye may become painful. Conservative treatments may be employed, but many eyes diagnosed at a late stage are eventually removed.

Many cases of Coats’ disease end up with a poor outcome and reduced vision. Many children present late in the course of the disease when significant retinal damage has already occurred. Prognosis is better when the disease is detected before permanent changes in the retina take place.

Leber’s congenital amaurosis

DEFINITION/OVERVIEW

Leber’s congenital amaurosis (LCA) is a group of recessively inherited congenital retinal dystrophies that result in severe visual impairment. Of patients with congenital blindness, the prevalence of LCA is thought to be 10–18%, making it one of the more common diagnoses of blindness in children. The incidence of this condition is 2–3 in 100,000. LCA is characterized by moderate to severe visual impairment identified at or within a few months of birth, infantile nystagmus, sluggish pupillary responses, and absent or poorly recordable electroretinographic (ERG) responses early in life.5

ETIOLOGY

LCA is an inherited, autosomal recessive (AR) disease, and the prevalence of LCA dramatically increases with consanguinity. LCA has been linked to numerous genes including GUCY2D (encoding RetGC-1) at 17p13.1, RPE65 at 1q31, CRX at 19q13.3, AIPLI at 17p13.1, TULP1 at 6p21.3, CRB1 at 1q31-3, and RPGRIP at 14q11.5,6 These mutations together account for about half of LCA patients.

The exact pathophysiologic pathways that lead to absent photoreceptor function have not been elucidated. The genes identified with LCA are expressed preferentially in the retina or the retinal pigment epithelium, and their functions are quite diverse and include retinal embryonic development (CRX), photoreceptor cell structure (CRB1), phototransduction (GUCY2D), protein trafficking (AIPL1, RPGRIP1), and vitamin A metabolism (RPE65).

CLINICAL PRESENTATION

Infants with LCA present with poor visual responses and often a large amplitude, roving nystagmus. Although not always seen, the oculodigital reflex (rubbing or poking at the eyes) is an ominous sign of poor vision in an infant, and is postulated to be an attempt to stimulate the retina by manual compression of the globe.

Visual acuity in early childhood ranges from 20/120–20/200, but progressively worsens to hand-motion or light perception by adolescence

or early adulthood. Other important clinical findings include minimally reactive pupils, high refractive error, and later, cataract, keratoconus, keratoglobus, and enopthalmos. By definition, LCA patients have no structural anomalies on ophthalmologic exam and have no known neurologic diseases. As the child matures, retinal changes often develop, most commonly chorioretinal pigmentation in the peripheral fundus of both eyes.

Systemic findings have been seen with higher frequency in LCA patients, including mental retardation (3–50%), medullary cystic kidney disease, cardiomyopathy, cerebellar vermis hypoplasia (10%), and neurosensory hearing loss (5–10%).5

DIFFERENTIAL DIAGNOSIS

The diagnosis of LCA cannot be differentiated from retinitis pigmentosa (RP), congenital stationary night blindness (CSNB) or achromatopsia on initial clinical examination. ERG is needed to determine the extent and relative decreased function of rods relative to cones; RP does not initially affect rods as severely as LCA, and both CSNB and achromatopsia affect cones more than rods.

DIAGNOSIS

LCA is diagnosed by first excluding all ocular and cerebral causes of poor vision. If the ocular exam is normal, then poor vision caused by damage to intracerebral visual pathways, including the optic tracts, optic radiations, and occipital lobe, should be evaluated by neurologic examination and magnetic resonance imaging (MRI). When ophthalmologic, neurologic, and radiographic

examinations are negative ERG is indicated to determine functionality of the photoreceptors and the bipolar retinal cells. ERG typically shows nonrecordable function or severely attenuated responses of both rods and cones. Visual evoked potential (VEP) testing may reveal some response in patients with no demonstrable ERG recordings.

Some patients with LCA will have subtle abnormalities in pigmentation of the central and peripheral fundus (10%) and/or macular dysplasia (10%) in infancy. As the child matures, the chorioretinal pigmentation often progresses, and optic nerve pallor and retinal arteriolar attenuation are commonly seen (169, 170).

MANAGEMENT/TREATMENT AND PROGNOSIS

There are no known treatments that halt the progression or improve the vision in patients with LCA. Due to the possibility of known systemic disorders occurring in conjunction with LCA, a full pediatric physical exam should be performed. Ancillary testing such as cardiac and renal ultrasonography may also be considered. An important intervention that can be very helpful for patients with LCA and their families is referral to early vision services in infancy, with continued low-vision therapy and services for school age children. Gene therapy is currently being studied in animal models. Because of genetic heterogeneity such treatments need to be tailored to the genetically defined subgroups.6

The appearance of the retina may undergo marked changes with age, but vision usually remains fairly stable through young adult life.

X-linked congenital stationary night blindness

DEFINITION/OVERVIEW

X-linked congenital stationary night blindness (CSNB) is a nonprogressive congenital dysfunction of rod photoreceptors leading to poor vision in dimly lit environments and varying degrees of visual impairment. It can be thought of as a problem with night vision. Three types of CSNB have been described and categorized according to the extent and type of rod photoreceptor dysfunction: complete and incomplete, and enhanced S-cone syndrome.

bright light stimulus causes dilation as opposed to the expected constriction of the pupil), which is characteristic of CSNB and achromatopsia. Myopic refractive errors are common, and hyperopia may occasionally be observed.

By definition, patients with CSNB have no structural anomalies on ophthalmologic exam and have no known neurologic diseases. The definitive diagnosis is by ERG, which shows an absent or varying degrees of low rod-mediated ‘b’ wave response compared with age-matched normal patients. The cone-mediated responses on ERG are normal. In contrast to LCA, no systemic disorders have been associated with X-linked or AR CSNB.7

DIFFERENTIAL DIAGNOSIS

ETIOLOGY

As its name implies, this condition is most commonly inherited as an X-linked disorder, specifically linked to Xp11. Both AR and autosomal dominant (AD) variants have been reported; patients with AD-inherited CSNB are not visually impaired. The complete type of CSNB has been linked to the NYX (nyctalopin) gene, and the incomplete type of CSNB has been linked to CACNA1F, both found on chromosome X. Enhanced S-cone syndrome has been linked to the gene NR2E3 at 15q23.6

Histopathologic studies have not revealed specific anatomic or functional abnormalities in patients with CSNB. ERG studies have suggested that the problem lies in communication synapses between outer retinal cells (attenuated ‘b’ wave). NYX, which encodes a glycosylphosphatidyl (GPI)- anchored protein called nyctalopin, is a unique member of the small leucine-rich proteoglycan (SLRP) family. The role of other SLRP proteins suggests that mutant nyctalopin disrupts developing retinal interconnections involving the optic nerve bipolar cells, leading to the visual losses seen in patients with complete CSNB.

CLINICAL PRESENTATION

Children with poor central vision may present with a sensory, roving nystagmus and poor visual attention and tracking. Visual acuity ranges from 20/20–20/200. The oculodigital reflex is an ominous sign of poor vision. Other important clinical findings include observation of a paradoxical pupillary response (direct,

The diagnosis of CSNB cannot be differentiated from Leber’s or achromatopsia on initial clinical examination of an infant. An ERG is needed to determine if the rods are affected relatively more than the cones (CSNB affects rods > cones, achromatopsia affects cones > rods), or if both types of photoreceptor are affected (LCA severely affects both rods and cones).

DIAGNOSIS

CSNB is diagnosed by first excluding all ocular causes of poor vision. Also, poor vision caused by damage to intracerebral visual pathways, including the optic tracts, optic radiations, and occipital lobe, should be evaluated by neurologic examination and MRI. When ophthalmologic (171, 172), neurologic, and radiographic examinations are negative, an ERG is indicated to determine relative functionality of the photoreceptors and the bipolar retinal cells. ERG typically shows nonrecordable function or severely attenuated responses of cone photoreceptors. No retinal pigmentary changes are seen in patients with CSNB.

MANAGEMENT/TREATMENT AND PROGNOSIS

There are no known treatments that improve the vision in patients with CSNB. An important intervention that can be very helpful for patients with CSNB and their families is low-vision therapy and social service referrals for infants and children with limited vision. Progression of vision loss is rarely seen in CSNB.