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

Abstract

PurposeTo assess relationships between structural and functional biomarkers, including new topographic measures of visual field sensitivity, in patients with autosomal dominant retinitis pigmentosa.MethodsSpectral 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.ResultsStructure-function relationships were accurately modeled (conditional R2>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 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.ConclusionsTopographic 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.

Morphologic characteristics and clinical significance of the macular‑sparing area in patients with retinitis pigmentosa as revealed by multicolor imaging

“…The results of the present study revealed a significant correlation between the size of macular-sparing area and BCVA. This is consistent with the results of previous studies, where ELM and EZ lines were identified as being significantly correlated with BCVA ( 5 , 22 , 23 ). Patients with advanced RP without outer retinal lines exhibit poorer BCVA.…”

Significant Relationship of Visual Field Sensitivity in Central 10° to Thickness of Retinal Layers in Retinitis Pigmentosa

“…On the other hand, the EZ and RPE are hyperreflective lines that can be easily distinguished in the OCT images, and the integrity of the EZ line has been described as an important marker of retinal function by numerous reports. 11,[22][23][24] These are the possible reasons for the OS thickness having the highest mR 2 . In addition, the statistical methods used in this study are different from those of the previous report with HFA 30-2; the past report used simple linear regression while we applied linear mixed-effects regression.…”

Biomarkers and Surrogate Endpoints in Drug Development: A European Regulatory View

“…8,9 Other studies have been performed to correlate EZ measurements with visual field measurements, 10,11 and it appears that the area around the edge of the EZ width represents the part of the retina that undergoes the most rapid rate of visual field loss. 10,12 Thus, there is scientific support for the concept of developing the EZ measurement as an endpoint for use in drug development. However, besides some concerns regarding the manual procedure to identify the zone and its fuzzy borders, there is yet insufficient information to conclude whether the EZ is a suitable endpoint to demonstrate efficacy in RP patients.…”