TY - JOUR
T1 - Structure-Function Modeling of Optical Coherence Tomography and Standard Automated Perimetry in the Retina of Patients with Autosomal Dominant Retinitis Pigmentosa
AU - EZ Working Group
AU - VPA Clinical Trial Study Group
AU - Smith, Travis B.
AU - Parker, Maria
AU - Steinkamp, Peter N.
AU - Weleber, Richard G.
AU - Smith, Ning
AU - Wilson, David J.
AU - Bernstein, Paul S.
AU - Birch, David G.
AU - Chiostri, Judith
AU - Erker, Laura R.
AU - Heckenlively, John R.
AU - Iannaccone, Alessandro
AU - Lam, Byron L.
AU - McCormack, Jennifer B.
AU - Pennesi, Mark E.
AU - Ferris, Frederick L.
AU - Francis, Peter J.
AU - Ho, Alexander
AU - Sadda, Srinivas R.
AU - Turner, F. Darell
AU - VanVeldhuisen, Paul C.
AU - Zilliox, Patricia
N1 - Funding Information:
One limitation of this study is that, because SAP was performed under photopic conditions, all functional biomarkers described here primarily represent cone function. Thus, comparisons with structural measures like the EZ width, which is supported by both cone and rod photoreceptors [], are purely observational. Previous structure-function studies [,–,] made similar comparisons with cone function from light-adapted SAP, and this methodology has practical advantages for retinal degeneration research []. Nonetheless, a more rigorous assessment would include subgrouping of patients based on electroretinogram findings to isolate those with diminished rod function or include rod-mediated functional measures from dark-adapted perimetry [], neither of which were available for this analysis.
Publisher Copyright:
© 2016 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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 R20.8 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 R2 = 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.
AB - 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 R20.8 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 R2 = 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.
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U2 - 10.1371/journal.pone.0148022
DO - 10.1371/journal.pone.0148022
M3 - Article
C2 - 26845445
AN - SCOPUS:84959441447
SN - 1932-6203
VL - 11
JO - PLoS One
JF - PLoS One
IS - 2
M1 - e0148022
ER -