Leber Congenital Amaurosis

Frequently Asked Questions (FAQs)

• What is Leber’s Congenital Amaurosis?
• What are the symptoms?
• When is it diagnosed?
• How quickly does it progress?
• How is it transmitted?
• Can it be treated?
• Who would be eligible for gene therapy?

What is Leber’s Congenital Amaurosis?

Leber’s Congenital Amaurosis is an inherited retinal degenerative disease characterised by severe loss of vision at birth.

What are the symptoms?

In addition to severe vision loss from birth, a variety of other eye-related abnormalities including roving eye movements, deep-set eyes, and sensitivity to bright light also occur with this disease. Some patients with LCA also experience central nervous system abnormalities such as developmental delay, epilepsy, and motor skill impairment. Because LCA is relatively rare, the frequency of central nervous system complications is unknown.

When is it diagnosed?

Within an infant's first few months of life, parents usually notice a lack of visual responsiveness and unusual roving eye movements, known as nystagmus. Eye examinations of infants with LCA reveal normal appearing retinas. However, electroretinography (ERG) tests, which measure visual function, detect little if any activity in the retina. A low level of retinal activity, measured by ERG, indicates very little visual function. ERG tests are essential for establishing a diagnosis of LCA.

How quickly does it progress?

Although the appearance of the retina undergoes marked changes with age, vision usually remains fairly stable through young adult life. Long term visual prognosis remains to be defined. Visual acuity in patients with LCA is usually limited to the level of counting fingers or detecting hand motions or bright lights. Some patients are also extremely sensitive to light (photophobia). Patients with remaining vision are often extremely farsighted.

How is it transmitted?

LCA is a genetic condition passed on by an autosomal recessive pattern of inheritance. However the causes of LCA are not well understood, researchers believe the disease may either be due to an abnormal development of photoreceptor cells in the retina or to an extremely premature degeneration of these cells.

Can it be treated?

Currently, there is no treatment for LCA in human patients. However, clinical trials in humans are expected to begin in the near future following the incredible success of research teams treating Briard dogs with a gene therapy.

In 1997, NEI researchers identified a gene causing LCA, named RPE65. As its name implies, the RPE65 gene is active in a layer of cells called the retinal pigment epithelium, or RPE for short. RPE cells support the function of photoreceptor cells in the neural retina.

Mutations in this gene were also identified as the cause of LCA in Briard dogs. In 2000, a team of researchers supported by the Foundation Fighting Blindness injected a single dose of a gene therapy treatment containing the RPE65 gene into three Briard dogs with LCA. Visual evaluation revealed the dogs had significant recovery of vision allowing them to avoid objects when walking and track movements. The dogs have retained their vision with no sign of complications.

Ever since this breakthrough, the team has worked to gain approval to begin human clinical trials.

Who would be eligible for gene therapy?

One of the challenges with this therapy is to determine how late in the disease process one can therapeutically intervene. Although mutations in the RPE65 gene cause severe vision loss, the structure of the retina remains intact for some indeterminate period of time. Eventually, however, retinal cells begin to die and at some point the disease is no longer treatable with gene therapy. Therefore, before a patient could enter a clinical trial it would have to be determined whether his/her retinas were still viable. Using high resolution imaging technology called Optical Coherence Tomography; NEI-supported researchers studied the structure of the retina of patients with LCA and controls without disease to determine whether it was possible to ascertain the health of the retina.

Adults with LCA had evidence of thinning in some portion(s) of the retina, indicating that some cell loss had occurred. The study authors found that for the therapy to b successful in adults with LCA, it will be necessary to target surviving tissue in the retina.