Estimating Normative Limits of Heidelberg Retina Tomograph Optic Disc Rim Area with Quantile Regression

Abstract

To investigate why the specificity of the Moorfields Regression Analysis (MRA) of the Heidelberg Retina Tomograph (HRT) varies with disc size, and to derive accurate normative limits for neuroretinal rim area to address this problem. Two datasets from healthy subjects (Manchester, UK, n = 88; Halifax, Nova Scotia, Canada, n = 75) were used to investigate the physiological relationship between the optic disc and neuroretinal rim area. Normative limits for rim area were derived by quantile regression (QR) and compared with those of the MRA (derived by linear regression). Logistic regression analyses were performed to quantify the association between disc size and positive classifications with the MRA, as well as with the QR-derived normative limits. In both datasets, the specificity of the MRA depended on optic disc size. The odds of observing a borderline or outside-normal-limits classification increased by approximately 10% for each 0.1 mm(2) increase in disc area (P < 0.1). The lower specificity of the MRA with large optic discs could be explained by the failure of linear regression to model the extremes of the rim area distribution (observations far from the mean). In comparison, the normative limits predicted by QR were larger for smaller discs (less specific, more sensitive), and smaller for larger discs, such that false-positive rates became independent of optic disc size. Normative limits derived by quantile regression appear to remove the size-dependence of specificity with the MRA. Because quantile regression does not rely on the restrictive assumptions of standard linear regression, it may be a more appropriate method for establishing normative limits in other clinical applications where the underlying distributions are nonnormal or have nonconstant variance.