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

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 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.
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.

### 研究目的
评估常染色体显性遗传性视网膜色素变性（autosomal dominant retinitis pigmentosa）患者的结构生物标志物与功能生物标志物之间的关联，其中包含新开发的视野敏感度地形测量指标。

### 研究方法
针对35例患者的60只眼，将光谱域光学相干断层扫描（spectral domain optical coherence tomography）线扫描图像与全视野标准自动视野检查所得的视野丘（hill of vision, HOV）敏感度表面进行半自动配准。从沿水平与垂直中线的视网膜外层b扫描中提取结构生物标志物；从b扫描对应的局部敏感度曲线以及全视野数据中提取功能生物标志物，其中包括功能过渡的地形测量指标，例如视野丘周围敏感度下降最快的轮廓，为便于表述，本文将其简称为HOV斜率。采用混合效应分析结合自动模型选择方法，通过决定系数（coefficient of determination, R²）对生物标志物间的关联进行两两评估。

### 研究结果
结构-功能关联可被精准建模（多数情况下条件决定系数R²>0.8）。水平方向生物标志物的最优拟合关联模型与相关模式，与垂直方向者存在差异。拥有最多显著功能关联的结构生物标志物为椭圆体带（ellipsoid zone, EZ）宽度，其次为感光细胞全层厚度。本研究中观测到的最强相关性见于椭圆体带宽度与HOV斜率距离之间（边际决定系数R²=0.85，p<10⁻¹⁰）。椭圆体带边缘处的平均敏感度缺损为7.6 dB。在所有功能生物标志物中，HOV斜率均值、HOV斜率平均距离以及b扫描上的最大敏感度，拥有最多的显著结构关联。

### 研究结论
地形斜率指标有望成为与过渡区相关的功能生物标志物；椭圆体带宽度与视野丘敏感度下降最快的位置存在强关联。