Leber Congenital Amaurosis (LCA)

Leber congenital amaurosis (LCA) is an inherited retinal degenerative disease characterized by severe loss of vision at 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.

Individuals with LCA have very reduced vision at birth. 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 key to establishing a diagnosis of LCA.

By early adolescence, various changes in the retinas of patients with LCA become readily apparent. Blood vessels often become narrow and constricted. A variety of pigmentary (color) changes can also occur in the retinal pigment epithelium (RPE), the supportive tissue underlying the retina. Sometimes, pigmentary changes are similar to another retinal degenerative disease known as retinitis pigmentosa.

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.

As of April 2008, there are three ongoing clinical trials of gene replacement therapy for LCA caused by mutations in the RPE65. They are similar therapies to the one that gave vision to 50 dogs, including the world-famous Lancelot, born blind from LCA. These studies provide extraordinary promise for eradicating LCA caused by RPE65, and eventually, LCA caused by other genetic variations.