Optical Gap Biomarker in Cone-Dominant Retinal Dystrophy

Am J Ophthalmol. 2020 Oct;218:40-53. doi: 10.1016/j.ajo.2020.05.016. Epub 2020 May 21.

Abstract

Purpose: To characterize the progression of optical gaps and expand the known etiologies of this phenotype.

Design: Retrospective cohort study.

Methods: Thirty-six patients were selected based on the identification of an optical gap on spectral-domain optical coherence tomography (OCT) from a large cohort of patients (N = 746) with confirmed diagnoses of inherited retinal dystrophy. The width and height of the gaps in 70 eyes of 36 patients were measured by 2 independent graders using the caliper tool on Heidelberg Explorer. Measurements of outer and central retinal thickness were also evaluated and correlated with gap dimensions.

Results: Longitudinal analysis confirmed the progressive nature of optical gaps in patients with Stargardt disease, achromatopsia, occult macular dystrophy, and cone dystrophies (P < .003). Larger changes in gap width were noted in patients with Stargardt disease (78.1 μm/year) and cone dystrophies (31.9 μm/year) compared with patients with achromatopsia (16.2 μm/year) and occult macular dystrophy (15.4 μm/year). Gap height decreased in patients with Stargardt disease (6.5 μm/year; P = .02) but increased in patients with achromatopsia (3.3 μm/year) and occult macular dystrophy (1.2 μm/year). Gap height correlated with measurements of central retinal thickness at the fovea (r = 0.782, P = .00012). Interocular discordance of the gap was observed in 7 patients. Finally, a review of all currently described etiologies of optical gap was summarized.

Conclusion: The optical gap is a progressive phenotype seen in an increasing number of etiologies. This progressive nature suggests a use as a biomarker in the understanding of disease progression. Interocular discordance of the phenotype may be a feature of Stargardt disease and cone dystrophies.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers*
  • Calcium-Binding Proteins / genetics
  • Child
  • Color Vision Defects / diagnostic imaging*
  • Color Vision Defects / physiopathology
  • Cone-Rod Dystrophies / diagnostic imaging*
  • Cone-Rod Dystrophies / physiopathology
  • Disease Progression
  • Electroretinography
  • Female
  • Humans
  • Macular Degeneration / diagnostic imaging*
  • Macular Degeneration / physiopathology
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Phenotype
  • Retina / physiopathology
  • Retinitis Pigmentosa / diagnostic imaging*
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / physiopathology
  • Retrospective Studies
  • Stargardt Disease / diagnostic imaging*
  • Stargardt Disease / physiopathology
  • Tomography, Optical Coherence*
  • Visual Acuity / physiology
  • rab GTP-Binding Proteins / genetics

Substances

  • Biomarkers
  • Calcium-Binding Proteins
  • Membrane Proteins
  • PITPNM3 protein, human
  • RAB28 protein, human
  • rab GTP-Binding Proteins

Supplementary concepts

  • Cone Dystrophy 3