Deep Scleral Exposure: A Degenerative Outcome of End-Stage Stargardt Disease

Am J Ophthalmol. 2018 Nov:195:16-25. doi: 10.1016/j.ajo.2018.07.018. Epub 2018 Jul 26.

Abstract

Purpose: To describe a distinct phenotypic outcome of outer retinal degeneration in a cohort of genetically confirmed patients with recessive Stargardt disease (STGD1).

Design: Retrospective case series.

Methods: Twelve patients, who were clinically diagnosed with STGD1 and exhibited a unique degenerative phenotype, were included in the study. Two disease-causing mutations were found in all patients by direct sequencing of the ABCA4 gene. Clinical characterization of patients were defined on fundus photographs, autofluorescence images (488-nm and 532-nm excitation), spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinogram (ffERG) testing.

Results: Mean age at initial presentation was 67.8 years and reported age of symptomatic onset was 14.1 years (mean disease duration = 53.8 years). Best-corrected visual acuity ranged from 20/400 to hand motion. All patients exhibited advanced degeneration across the posterior pole resulting in a reflectively pale, blonde fundus owing to unobstructed exposure of the underlying sclera. SD-OCT revealed complete loss of the outer retinal bands (external limiting membrane, ellipsoid zone, interdigitation zone, and retinal pigment epithelium) and choroidal layers. Scotopic and photopic waveforms on ffERG were nonrecordable or severely attenuated in 8 patients who were tested.

Conclusions: Widespread scleral exposure is a clinical outcome in a subset of STGD1 following a long duration of disease progression (∼50 years). The blonde fundus in such cases may exhibit phenotypic overlap and shared therapeutic implications with other aggressive chorioretinal dystrophies such as end-stage choroideremia, gyrate atrophy, or RPE65-Leber congenital amaurosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Aged
  • Aged, 80 and over
  • Autogenic Training
  • Color Vision / physiology
  • Electroretinography
  • Female
  • Fluorescein Angiography / methods
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Macular Degeneration / congenital*
  • Macular Degeneration / diagnosis
  • Macular Degeneration / genetics
  • Macular Degeneration / physiopathology
  • Male
  • Middle Aged
  • Night Vision / physiology
  • Optical Imaging
  • Phenotype
  • Retina / physiopathology
  • Retinal Degeneration / diagnosis*
  • Retinal Degeneration / genetics
  • Retinal Degeneration / physiopathology
  • Retrospective Studies
  • Stargardt Disease
  • Tomography, Optical Coherence / methods
  • Visual Acuity / physiology

Substances

  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters