Structure-Function Modeling of Optical Coherence Tomography and Standard Automated Perimetry in the Retina of Patients with Autosomal Dominant Retinitis Pigmentosa

PLoS One. 2016 Feb 4;11(2):e0148022. doi: 10.1371/journal.pone.0148022. eCollection 2016.

Abstract

Purpose: To assess relationships between structural and functional biomarkers, including new topographic measures of visual field sensitivity, in patients with autosomal dominant retinitis pigmentosa.

Methods: Spectral domain optical coherence tomography line scans and hill of vision (HOV) sensitivity surfaces from full-field standard automated perimetry were semi-automatically aligned for 60 eyes of 35 patients. Structural biomarkers were extracted from outer retina b-scans along horizontal and vertical midlines. Functional biomarkers were extracted from local sensitivity profiles along the b-scans and from the full visual field. These included topographic measures of functional transition such as the contour of most rapid sensitivity decline around the HOV, herein called HOV slope for convenience. Biomarker relationships were assessed pairwise by coefficients of determination (R2) from mixed-effects analysis with automatic model selection.

Results: Structure-function relationships were accurately modeled (conditional R(2)>0.8 in most cases). The best-fit relationship models and correlation patterns for horizontally oriented biomarkers were different than vertically oriented ones. The structural biomarker with the largest number of significant functional correlates was the ellipsoid zone (EZ) width, followed by the total photoreceptor layer thickness. The strongest correlation observed was between EZ width and HOV slope distance (marginal R(2) = 0.85, p<10(-10)). The mean sensitivity defect at the EZ edge was 7.6 dB. Among all functional biomarkers, the HOV slope mean value, HOV slope mean distance, and maximum sensitivity along the b-scan had the largest number of significant structural correlates.

Conclusions: Topographic slope metrics show promise as functional biomarkers relevant to the transition zone. EZ width is strongly associated with the location of most rapid HOV decline.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Biomarkers
  • Genes, Dominant
  • Humans
  • Models, Theoretical
  • Retina / pathology*
  • Retina / physiopathology*
  • Retinitis Pigmentosa / diagnosis*
  • Retinitis Pigmentosa / genetics*
  • Tomography, Optical Coherence / methods*

Substances

  • Biomarkers

Grants and funding

This work was supported by Maryrose Sylvester and the Foundation Fighting Blindness Clinical Research Institute (FFB-CRI). The VPA Clinical Trial is co-sponsored by the FFB-CRI and the Department of Defense (W81XWH-09-2-0189). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.