Leber Congenital Amaurosis

First described in 1869 by Theodore Leber.

• Congenital or Early infancy non-syndromic retinal blindness
• Searching nystagmus
• Abnormal pupil reponses
• “oculodigital sign”- digital eye pressure to induce retinal response
• Fundus appearance:
  • Initially can have normal fundus appearance followed by pigmentary changes in the retina, vascular attenuation and optic nerve pallor.
  • Bone spicules in macula and periphery
  • Loss of retinal lamination and photoreceptor loss
  • Exudative type retinopathy in CRB1-assoicated disease
  • RPE65-related disease usually has milder peripheral RPE mottling and white dots
• Disc drusen or pseudopapilledema

• Severe visual impairment from birth or first few months of life
• Fundus appearance
  • may be normal
  • Vessel attenuation, disc pallor, peripheral retinal pigmentation
• ERG is undetectable

• Achromatopsia
• Congenital Stationary Night Blindness
• Retinitis Pigmentosa
• Idiopathic Nystagmus Syndrome

• 70% of patients have a known genetic variant io one of the following genes that preferentially are expressed in the retina or RPE
• Autosomal Recessive
  • AIPL1, ALMS1, CEP290, CRB1 (photoreceptor cell structure), GUCY2D (Protein trafficking), IMPDH1, LCA5, LRAT (visual cycle function), MERTK, RD3 ,RDH12, RPGRIP1, RPE65 (visual cycle function), SPATA7, KCNJ13, ICQB1, NMNAT1, and TULP1
• Autosomal Dominant: CRX - photoreceptor cell development

• Gene replacement therapy with Luxturna (vortigene neparvovec-rzyl)
  • Adeno-associated virus vector administered subretinally

1. Taylor and Hoyt chapter 46. Leger congenital amaurosis.