STARGARDT DISEASE

Stargardt disease is a common inherited retinal disorder. It typically affects young, healthy individuals in the first or second decade of life. Stargardt disease is usually autosomal recessive, but autosomal dominant and mitochondrial pedigrees have been described.

Symptoms

Individuals with Stargardt disease experience bilateral visual loss in childhood or young adulthood. Visual complaints may be disproportionate to the clinical findings—particularly early in the course of the disease. Other symptoms include dyschromatopsia, central scotomas, or photophobia.

Clinical Features

There is a wide spectrum of clinical findings in Stargardt disease. Initially, the fundus may appear normal. The macula may have a vermilion discoloration as the heavily pigmented retinal pigment epithelium (RPE) obscures the underlying choroidal details. Yellowish “flecks” may be visualized at the level of the RPE. The flecks are variable in size, shape, and distribution but are usually symmetric between eyes. The flecks have a triradiate or pisciform (fish-tail) configuration. The flecks tend to fade over time, often replaced by RPE atrophy. Macular alterations range from mild RPE mottling to marked geographic atrophy. The fovea may develop a “beaten metal” appearance or a “bull’s eye” pattern of atrophy. Rarely, choroidal neovascularization and midperipheral RPE hyperplasia are seen.

Ancillary Testing

The classic fluorescein angiographic finding is a “silent choroid” distinguished by blockage of choroidal fluorescence. Hyperfluorescence in the macula is variable, depending on the degree of RPE atrophy. Flecks usually do not hypoor hyperfluoresce; however, when the flecks are associated with RPE atrophy, an irregular pattern of hyperfluorescence may be seen.

Electrophysiologic testing is usually normal but may be abnormal in advanced cases with more widespread flecks or RPE abnormalities. Abnormalities in the pattern electroretinogram are common.

Pathology/Pathogenesis

Mutations in the adenosine triphosphate (ATP)-binding cassette transporter gene (ABCA4, formerly known as ABCR) have been identified in Stargardt disease.

Stargardt disease is characterized by accumulation of lipofuscin-like material in the RPE. Lipofuscin accumulation may result from abnormal photoreceptor degradation. Other histopathologic findings include heterogeneity of RPE cells, loss of photoreceptors,

and Müller cell hypertrophy.

Treatment/Prognosis

There is no known treatment for Stargardt disease. The visual prognosis depends on the degree of macular involvement. Vision usually stabilizes in the 20/200

range when affected. Low-vision aids are very effective. Laser therapy may be helpful for those rare cases of choroidal neovascularization.

Systemic Evaluation

There are no known systemic associations of Stargardt disease.

Stargardt disease is characterized by the presence of numerous yellowish “flecks” located at the level of the retinal pigment epithelium. The flecks are variable in size, shape, and distribution but are usually symmetric between eyes.

Macular alterations range from mild retinal pigment epithelial mottling to marked geographic atrophy. In some patients, the macula has a “beaten metal” appearance.

The flecks have a triradiate or pisciform (fish-tail) configuration. They may be widespread or concentrated in the macula. The flecks tend to fade over time, often replaced by retinal pigment epithelium atrophy.

Stargardt disease must be considered in patients with a bull’s eye maculopathy. The bull’s eye maculopathy results from atrophy of the retinal pigment epithelium.

Fluorescein angiogram of 6-year-old girl with Stargardt disease. The characteristic “silent choroid” is observed in the peripheral macula. This relative hypofluorescence is the result of the lipofuscin-laden retinal pigment epithelial cells blocking the underlying choroidal fluorescence.

The central hyperfluorescence observed in each eye is the result of retinal pigment epithelial atrophy.

X-LINKED JUVENILE RETINOSCHISIS

X-linked juvenile retinoschisis is a vitreoretinal dystrophy that occurs in the male population. Patients affected with this X-linked recessive condition present with symptoms in early childhood.

Symptoms

Individuals with X-linked retinoschisis usually experience mild or moderate visual loss. Progression of the condition occurs mainly in the first years of life and then stabilizes or progresses at a much slower rate. Visual acuity may range from 20/50 to 20/400.

Clinical Features

X-linked retinoschisis is characterized by a stellate maculopathy. This foveal schisis is found in almost all patients. However, adult patients may have atrophic retinal pigment epithelial (RPE) changes following the disappearance of this classic foveal cystic appearance. Peripheral retinoschisis occurs in about 50% of affected patients. The most common location for this peripheral schisis is the inferotemporal quadrant. This retinal splitting occurs at the nerve fiber layer level. Other findings include holes in the inner retinal layer, retinal dragging, vitreous strands, and sheathing of vessels. The clinical course of these patients could be complicated by the development of vitreous hemorrhage and rhegmatogenous retinal detachments. Hypermetropia, strabismus, nystagmus, and cataracts may be present in this dystrophy.

Ancillary Testing

X-linked retinoschisis may present a fluorescein angiographic pattern similar to that of cystoid macular edema. However, the late phases do not reveal leakage of dye. In some patients, the retinal vessels from the peripheral schisis areas may leak on fluorescein angiography.

Visual field testing demonstrates an absolute scotoma that corresponds to the areas of peripheral schisis. The electroretinogram (ERG) shows a reduced b-wave amplitude in photopic and scotopic conditions. The oscillatory potentials of the photoreceptors are reduced, and the implicit times are prolonged.

Pathology/Pathogenesis

The X-linked retinoschisis gene (XLRS1) has been mapped to Xp 22.2. This gene encodes retinoschisin, a photoreceptor protein secreted into the inner retina. A diffuse abnormality of the Müller cells may be the

underlying cause of this condition, as suggested by ERG and histopathologic findings.

Treatment/Prognosis

Affected patients usually maintain stable visual acuity or experience a slow progression of the condition. However, if complications such as vitreous hemorrhage or retinal detachment arise, surgical management may be necessary. Hence, patients with X-linked retinoschisis should be observed.

Systemic Evaluation

No known systemic associations have been reported with this condition.

X-linked juvenile retinoschisis is characterized by cyst-like changes in the fovea. The splitting of the neurosensory retina occurs between the nerve fiber and ganglion cell layers.

This 51-year-old man with X-linked juvenile retinoschisis had extensive macular pigmentary alterations and sheathing of the retinal vessels.

Higher magnification of the macula of the patient shown in the previous figure reveals the stellate, cyst-like pattern of schisis extending from the center of the fovea.

His left eye had similar findings. Note the white “fishbone” spicules that may be seen in patients with X-linked juvenile retinoschisis.

Peripheral retinoschisis may contain inner or outer retinal holes. Vitreous hemorrhage or retinal detachment may cause visual loss in patients with X-linked juvenile retinoschisis.

Peripheral retinoschisis may extend to the macula. This 9-year-old boy had a retinal fold extending through the macula. He also had retinal pigment epithelial alterations in the macula and peripheral retina.

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Dominant Drusen

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Gyrate Atrophy

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Leber’s Congenital Amaurosis

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North Carolina Macular Dystrophy

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Retinitis Pigmentosa (Rod-Cone Dystrophies)

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Sorsby’s Fundus Dystrophy

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Stargardt Disease

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X-Linked Juvenile Retinoschisis

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