Hereditary Retinal Disorders

ALBINISM

Albinism is caused by an inborn error of metabolism and is classified as oculocutaneous albinism and ocular albinism. Oculocutaneous albinism is usually an autosomal recessive condition. However, autosomal dominant transmission can occur. Ocular albinism is commonly an X-linked disease.

Symptoms

Patients affected with albinism typically experience subnormal visual acuity and photophobia.

Clinical Features

Individuals with oculocutaneous and ocular albinism show nystagmus, iris transillumination defects, hypopigmented fundus, and foveal hypoplasia. Other ocular findings include strabismus, myopia, and astigmatism. In addition to the ocular features, persons affected with oculocutaneous albinism show decreased pigmentation in hair and skin. Tyrosinase-negative patients lack pigmentation entirely, while tyrosinase-positive patients have variable pigmentation.

Ancillary Testing

Tyrosinase hair bulb testing helps to classify oculocutaneous albinism as tyrosinase positive and tyrosinase negative. However, there are several subtypes among both tyrosinase-negative and tyrosinase-positive oculocutaneous albinism. The majority of patients with oculocutaneous albinism and ocular albinism have normal electroretinographic findings.

Pathology/Pathogenesis

In albinism the production of melanin is affected. Histopathologic reports demonstrate absence of the foveal pit. In oculocutaneous albinism the quantity of melanin in the melanosomes is reduced. Ocular albinism has a diminished amount of melanosomes.

Treatment/Prognosis

There is no known treatment for albinism.

Systemic Evaluation

Oculocutaneous albinism can be associated with several systemic findings. Impairment of the reticuloendothelial system, with subsequent susceptibility to infections and an increased risk of development of lymphoreticular malignancies, is seen in Chédiak-Higashi syndrome. This form of oculocutaneous albinism is inherited as an autosomal recessive trait and can be fatal. HermanskyPudlak syndrome is characterized by abnormal platelets and bleeding, and easy bruising can occur as a result. The majority of these patients are from Puerto Rico. Due to the potential mortality associated with these conditions, it is extremely important to consult a hematologist if any of these syndromes is suspected.

Oculocutaneous albinism is characterized by iris transillumination. The outlines of the lens and ciliary processes are visible through this nondilated pupil.

This 9-year-old girl had oculocutaneous albinism with nystagmus, high myopia, and visual acuity of 20/400.

Ophthalmoscopic examination reveals a hypopigmented fundus. The larger choroidal vessels are visible through the hypopigmented retinal pigment epithelium.

Both eyes demonstrated hypopigmentation of the fundus and foveal hypoplasia, with lack of the normal foveal reflex.

BEST’S DISEASE

Best’s disease is an autosomal dominantly inherited macular dystrophy. Patients with Best’s disease usually retain reading vision during adult life in at least one eye.

Symptoms

Individuals with Best’s disease or vitelliform macular dystrophy experience mild visual loss. This visual loss occurs slowly throughout the years. Other complaints include metamorphopsia and central scotomas.

Clinical Features

Best’s macular dystrophy is characterized by a yellow, egg yolk-like lesion at the level of the retinal pigment epithelium. This lesion is usually detected in infancy or childhood. Vitelliform lesions are typically bilateral and symmetric, ranging from 0.5 disc diameter (DD) to 2 DD in dimension. It is not unusual to visualize multifocal vitelliform lesions in this dystrophy. The vitelliform lesion becomes disrupted and reabsorbs with time, producing the pseudohypopyon and scrambled egg stages. Eventually, an area of atrophy develops. Some patients develop choroidal neovascularization and experience further decrease in visual acuity.

Ancillary Testing

Fluorescein angiography reveals a blockage of the choroidal fluorescence by the vitelliform lesion. As the condition progresses, evolving into the atrophic stage, retinal pigment epithelial atrophic areas develop. These areas appear as hyperfluorescent window defects by fluorescein angiography.

A normal electroretinogram (ERG) in conjunction with an abnormal electro-oculogram (EOG) characterizes Best’s disease. The EOG light to dark ratio (Arden ratio) is usually below 1.5. This electrophysiologic test plays an important role in the diagnosis of this condition, as patients without the characteristic fundus lesion can have abnormal EOG findings.

Pathology/Pathogenesis

The genetic defect causing Best’s disease has been mapped to chromosome 11q13. The gene causing Best’s disease has been designated vitelliform macular dystrophy type 2 gene (VMD2). VMD2 encodes a transmembrane protein of RPE cells, known as bestrophin, involved in the transport of polyunsaturated fatty

acids in the retina. Best’s disease is characterized by an underlying retinal pigment epithelial abnormality. Histopathologic reports show accumulation of lipofuscin within retinal pigment epithelial cells However, no histopathologic studies have described

the vitelliform stage.

Treatment/Prognosis

There is no treatment for Best’s disease. Nevertheless, if choroidal neovascularization develops, certain therapeutic regimens such as laser photocoagulation, photodynamic therapy, and submacular surgery may

be considered.

Systemic Evaluation

There are no known systemic findings associated with Best’s disease.

Best’s disease is characterized by a “sunny side up,” yellow egg yolk-like lesion at the level of the retinal pigment epithelium. Visual acuity in this stage is usually normal or only mildly reduced.

The “pseudohypopyon” stage of Best’s disease is characterized by liquefaction of the vitelliform material, producing a boat-like lesion in the macula.

Most cases of Best’s disease have a solitary lesion in the center of the macula of each eye, as shown in the previous figure. However, the disease may be asymmetric or have mutifocal lesions, as demonstrated here.

As the retinal pigment epithelium atrophies, the lesion develops a “scrambled egg” appearance.

Visual loss is related to atrophy or the development of choroidal neovascularization. This fundus photograph demonstrates atrophy and retinal pigment epithelial hyperplasia.

Patients with Best’s disease may develop choroidal neovascularization. Signs of choroidal neovascularization include subretinal blood and subretinal fluid.