Leber Congenital Amaurosis (LCA)

Inherited degenerative disease of the retina characterized by severely decreased vision manifesting at birth or shortly thereafter. Other ocular anomalies may include sensory (wandering) nystagmus, amaurotic pupils, deep-set eyes, and photophobia. Central nervous system anomalies have been described in some patients. Do not confuse with Leber hereditary optic neuropathy (see Leber Hereditary Optic Neuropathy).

First described by the German ophthalmologist Theodor von Leber in 1869.

Approximately 3:100,000 neonates are born with this autosomal recessive transmitted disorder. Nine genetic loci for LCA have been discovered, of which six genes have identified. LCA is now no longer considered one disorder but rather multiple disorders, which can be classified into three different categories: (1) aplasia, resulting in abnormal embryologic formation of photoreceptors; (2) early degeneration of photoreceptors with progressive cell death; and (3) dysfunction of the photoreceptors with normal retinal anatomy.

Vision is already significantly reduced at birth or shortly thereafter. Sensory (wandering) nystagmus and lack of visual responsiveness alert the parents, usually within the first months of life. Initial examination may reveal a normal retina and a fundus appearance that either is essentially normal or reveals a progressive pigmentary retinopathy. The pupils are amaurotic and the eyes deep sunken. However, the final diagnosis is made by electroretinography, which shows only small (at high intensities) or no photopic responses. Both cone and rod responses are affected. Patients are described as frequently poking and rubbing their eyes (the so-called “Oculodigital Reflex” of Leber and Franceschetti), which is not specific to LCA because it is observed in other forms of amaurosis (Leber was the first to describe this phenomenon). Other associated ocular features may include ptosis, strabismus, keratoconus/keratoglobus, cataracts, microphthalmos, macular coloboma, pigmentary retinopathy and maculopathy, optic disc edema, retinal vascular changes, and high-grade hyperopia or myopia (less common). By early adolescence, the retina of LCA patients may undergo significant changes. Retinal blood vessels often become narrow and constricted, and pigmentary changes similar to those found in retinitis pigmentosa may affect the retinal pigment epithelium. Despite these changes, vision does not usually deteriorate further. Visual acuity in LCA patients is most often limited to the level of finger counting or detection of bright light. Some patients are extremely photophobic. At this time, no treatment is available; however, current research is focusing on gene therapy. On rare occasion, LCA is associated with central nervous system symptoms such as delayed psychomotor development and seizures.

In patients with isolated LCA (i.e., not associated with a syndrome or central nervous system findings), no specific anesthetic concerns should arise from this disorder. In the presence of seizures, keep in mind that antiseizure medications can alter the metabolism and elimination of anesthetic drugs. Cooperation of mentally delayed patients may be limited. Sedative and/or hypnotic premedication and the presence of the primary caregiver may be helpful during induction of anesthesia. Dealing with a blind patient who cannot see what is happening requires more explicit explanations in general and particularly warnings before painful procedures. Severely photophobic patients will appreciate having the operating theater lights dimmed during induction and emergence of anesthesia and afterward in the postanesthesia care unit. In cases where LCA is part of a syndrome, the specific anesthetic considerations for that syndrome apply.

Cone-Rod Retinal Dystrophies: Inherited dystrophy of retinal photoreceptors and pigment epithelium; simultaneous abiotrophic degeneration of rods and cones.

LCA can be associated with the following syndromes:

Alström Syndrome: Inherited syndrome with diabetes mellitus, cardiac, hepatic, and renal involvement and progressive visual and hearing loss.

Bardet-Biedl Syndrome: Mental retardation, pigmentary retinopathy, polydactyly, obesity, renal anomalies, and hypogenitalism.

Joubert Syndrome: Genetic disorder characterized by cerebral malformations (vermis and brainstem) resulting in severe coordination (ataxia) and breathing (sleep apnea, hyperpnea) disorders.

Neuronal Ceroid Lipofuscinoses (NCLs): Hereditary progressive neurodegenerative disorders with mental retardation, visual loss, and seizures. The NCLs are probably the most common class of neurodegenerative disease in children.

Loken Senior Syndrome: Inherited disorder characterized by rapidly progressive renal insufficiency (nephronophthisis) and eye disease (retinitis pigmentosa).

Zellweger Syndrome: Disorder characterized by the congenital absence of functioning peroxisomes (cellular structures responsible for elimination of toxic substances) resulting in a cerebrohepatorenal syndrome. The disease affects brain development, particularly myelination. Most important features include hepatomegaly, polycystic kidney disease, visual disturbances, and high plasma levels of iron and copper. Other features include muscular hypotonia already noticeable at birth, mental retardation, seizures, coagulopathy, and dysphagia with recurrent aspiration. Congenital heart defects have been described. Life expectancy is approximately 6 months.