Leber's congenital amaurosis (LCA) is an inherited retinal disease which occurs at birth and is characterized by loss of vision. It is an autosomal recessive disorder caused by abnormal development of photoreceptor cells (cones and rods of the retina). Thus, Leber's congenital amaurosis is a severe dystrophy of the retina, which becomes evident in the first year of life. Visual function is usually poor and often accompanied by nystagmus (roving eye movements), sluggish or near-absent pupillary responses, photophobia, high hyperopia, and keratoconus. Visual acuity is rarely better than 20/400.
Eye examinations of infants with Leber's congenital amaurosis reveal normal appearing retinas. Nevertheless, 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 Leber's congenital amaurosis.
Fourteen genes have been identified with mutations that can each cause Leber's congenital amaurosis. These genes account for approximately 75 percent of all cases of LCA. With this information, scientists are better equipped to develop preventions and treatments. Gene therapy treatments are still in the trial phase but there have been successes. The results of a phase 1 trial conducted, by the University of Pennsylvania and Children’s Hospital of Philadelphia and published in 2009, showed sustained improvement in 12 subjects with RPE65-associated Leber's congenital amaurosis after treatment with AAV2-hRPE65v2, a gene replacement therapy.