Recessive Stargardt disease phenocopying hydroxychloroquine retinopathy

Graefes Arch Clin Exp Ophthalmol. 2016 May;254(5):865-72. doi: 10.1007/s00417-015-3142-8. Epub 2015 Aug 28.

Abstract

Purpose: To describe a series of patients with Stargardt disease (STGD1) exhibiting a phenotype usually associated with hydroxychloroquine (HCQ) retinopathy on spectral domain-optical coherence tomography (SD-OCT).

Methods: Observational case series from Columbia University Medical Center involving eight patients with genetically-confirmed STGD1. Patients selected for the study presented no history of HCQ use. Horizontal macular SD-OCT scans and accompanying 488-nm autofluorescence (AF) images, color fundus photographs, and full-field electroretinograms were analyzed.

Results: All study patients exhibited an abrupt thinning of the parafoveal region or disruption of the outer retinal layers on SD-OCT resembling the transient HCQ retinopathy phenotype. Funduscopy and AF imaging revealed variations of bull's eye maculopathy (BEM). Five patients exhibited local fleck-like deposits around the lesion. Genetic screening confirmed two disease-causing ABCA4 mutations in five patients and one mutation in three patients.

Conclusions: A transient SD-OCT phenotype ascribed to patients with HCQ retinopathy is associated with an early subtype of STGD1. This finding may also present with HCQ retinopathy-like BEM lesions on AF imaging and funduscopy. A possible phenotypic overlap is unsurprising, given certain shared mechanistic disease processes between the two conditions. A thorough work-up, including screening of genes that are causal in retinal dystrophies associated with foveal sparing, may prevent misdiagnosis of more ambiguous cases.

Keywords: ABCA4; Hydroxychloroquine toxicity; Phenocopy; Stargardt disease.

Publication types

  • Observational Study

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Adult
  • Antimalarials / toxicity*
  • Child
  • Electroretinography
  • Female
  • Genes, Recessive
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Hydroxychloroquine / toxicity*
  • Macular Degeneration / congenital*
  • Macular Degeneration / diagnosis
  • Macular Degeneration / genetics
  • Male
  • Middle Aged
  • Mutation
  • Phenotype
  • Retinal Diseases / chemically induced
  • Retinal Diseases / diagnosis*
  • Retrospective Studies
  • Stargardt Disease
  • Tomography, Optical Coherence
  • Young Adult

Substances

  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters
  • Antimalarials
  • Hydroxychloroquine