Bernd Wissinger

Establishing baseline rod electroretinogram values in achromatopsia and cone dystrophy

PurposeTo establish the normal range of values for rod-isolated b-wave amplitudes in achromatopsia and cone dystrophies.MethodsWe reviewed charts of 112 patients with various types of cone dystrophy, and compared their standardized electroretinographic rod b-wave amplitudes with age-matched normal controls. Twenty-six patients had known mutations in achromatopsia and cone dystrophy genes, while 53 were characterized by their inheritance pattern since they had yet to have their gene identified. Visual acuity information and scotomata were documented.ResultsWe found that patients with achromatopsia and cone dystrophy had rod b-wave amplitudes that were significantly lower than age-matched controls, but found no evidence of rod amplitude progression nor loss of peripheral visual fields in the study group.ConclusionsWe found that cone dystrophy patients of all types had depressed rod-isolated ERGs across the board. If typical diagnostic criteria are used, these patients might be considered to have “abnormal” rod-isolated electroretinographic values, and might be called “cone-rod dystrophy”, even though the waveforms are stable for years. Patients with cone-rod dysfunction patterns on ERG can be better understood by also performing kinetic (Goldmann) visual fields, which will help to distinguish cone dystrophies from progressive cone-rod dystrophies by central scotomata size and progression over time in many forms of cone-rod dystrophy.

The Molecular Basis of Achromatopsia

Achromatopsia is a rare genetic heterogenic disorder with known loci on chromosome 2q11 (ACHM2) and chromosome 8q21 (ACHM3). These loci encode the genes for the channel-forming α- (CNGA3) and the modulatory (β-subunit (CNGB3) of the cone photoreceptor cGMP gated channel — the final component of the cone photoreceptor transduction cascade. Candidate gene screening of these genes in patients affect by Achromatopsia resulted in the identification of a large number of predominantly missense mutations in the CNGA3 gene and a discrete number of mostly nonsense mutations in the CNGB3 gene. Mutations in both genes result in Achromatopsia with clinically indistinguishable phenotypes.