How to explain “flat” electroretinograms when patients with Leber's congenital amaurosis aren't blind

Abstract

PurposeTo explain how a ‘flat” or ‘extinguished” electroretinogram (ERG) in a patient with Leber's congenital amaurosis may not necessarily be indicative of a corresponding loss of vision.MethodsBasic principles of ocular as well as auditory electrophysiology, wave physics, phototransduction metabolic pathways and ophthalmic genetics were reviewed and organized to reveal heretofore overlooked pathways. Correlations of ocular as well as auditory electrophysiology characteristics for Leber's congenital amaurosis and congenital auditory neuropathy/dys‐synchrony were made.ResultsVariably delayed individual photoreceptor cell signaling secondary to metabolic enzymatic deficiencies involved in phototransduction results in ERG a‐waves produced, and subsequent b‐waves, to interfere destructively with each other, rather than allow for averaging in‐phase summation to permit recordable ERG signals. Despite the delayed visual cycle, intraretinal synaptic transmission may proceed uninhibited to activate retinal ganglion cells and axonal pathways to the visual cortex.ConclusionsA ‘flat” or ‘extinguished” ERG need not indicate absent vision, but overall destructive interference of individual a‐waves and b‐waves averaged for the recorded ERG. Analogous auditory electrophysiologic findings are noted in corresponding so‐called congenital auditory neuropathy/dys‐synchrony. Such findings are of great diagnostic utility and may be considered pathognomonic. Theoretically, the stability or progression of a patient with Leber's congenital amaurosis, and their response to an interventional genetic or pharmacologic therapeutic regimen, could be followed in more sensitive and objective manner at the cellular level via electro‐oculography, prior to visual acuity, visual evoked potentials, or ERG testing revealing any changes in overall retinal function.