Early impairment of the full-field photopic negative response in patients with Stargardt disease and pathogenic variants of the ABCA4 gene

Clin Exp Ophthalmol. 2018 Jul;46(5):519-530. doi: 10.1111/ceo.13115. Epub 2017 Dec 28.


Background: To study the photopic negative response of the full-field photopic electroretinography (ERG) in Stargardt patients with pathogenic variants in the ABCA4 gene.

Methods: A retrospective analysis of 35 Stargardt patients with ABCA4 gene pathogenic variants, compared to normal age-matched controls. Patients were clinically followed at the Ophthalmology Department of Fondazione Policlinico Universitario A. Gemelli/Università Cattolica del Sacro Cuore, Rome, Italy.

Results: The photopic negative response of the full-field photopic ERG was compromised in most Stargardt patients. In the presence of a normal B-wave, the amplitude ratio between the photopic negative response and the B-wave displayed a 97% accuracy in detecting diseased eyes (receiver operating characteristic curves).

Conclusions: In Stargardt patients with ABCA4 pathogenic mutations, the photopic negative response of the full-field photopic ERG is a very sensitive disease read-out. Its inclusion in standard ERG analysis would be a no-cost addition of practical consequence in the follow-up of Stargardt disease. The early impairment of the photopic negative response suggests that inner retinal function might be affected in Stargardt disease earlier than previously acknowledged.

Keywords: Stargardt disease; photopic electroretinography; photopic negative response; retina.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Adolescent
  • Adult
  • Child
  • DNA / genetics*
  • Electroretinography / methods*
  • Female
  • Follow-Up Studies
  • Humans
  • Macular Degeneration / congenital*
  • Macular Degeneration / diagnosis
  • Macular Degeneration / genetics
  • Macular Degeneration / physiopathology
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • ROC Curve
  • Retrospective Studies
  • Rod Cell Outer Segment / physiology
  • Stargardt Disease
  • Time Factors
  • Tomography, Optical Coherence
  • Visual Acuity / physiology*
  • Young Adult


  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters
  • DNA

Supplementary concepts

  • Stargardt disease 1