Defining Glaucomatous Optic Neuropathy from a Continuous Measure of Optic Nerve Damage – The Optimal Cut-off Point for Risk-factor Analysis in Population-based Epidemiology

Abstract

Purpose: Diseases characterized by a continuous trait can be defined by setting a cut-off point for the disease measure in question, accepting some misclassification. The 97.5th percentile is commonly used as a cut-off point. However, it is unclear whether this percentile is the optimal cut-off point from the point of view of risk-factor analysis. The optimal cut-off point for risk-factor analysis can be found with a statistical method that minimizes the effect of misclassification. We applied this method to glaucomatous optic neuropathy. Here, the continuous trait is the cup-disc ratio. The aim of this study was to determine the optimal cup-disc ratio cut-off point for risk-factor analysis in population-based epidemiology.

Methods: All participants in the population-based Rotterdam Study underwent intraocular pressure (IOP) measurements, assessment of the cup-disc ratio with the Heidelberg Retina Tomograph (HRT) and visual field testing. In the statistical method, the cup-disc ratio (the continuous trait) and the IOP (a major risk factor) were independent variables and glaucomatous visual field loss (the true glaucoma endpoint) the dependent variable in a logistic regression model. The optimal cup-disc ratio cut-off point was found by minimizing the influence of IOP in this model. Variability of the approach was assessed by using a bootstrap resampling technique.

Results: Of 2444 included participants, 93 had glaucomatous visual field loss. The median optimal cup-disc ratio cut-off point was the 97.0th percentile with a 95% central range from 95.5 to 98.5.

Conclusion: The optimal cup-disc ratio cut-off point for risk-factor analysis is close to the commonly used 97.5th percentile.

Keywords::

• Cut-off point
• Percentile
• Epidemiology
• Bootstrap
• Heidelberg Retina Tomograph
• Glaucomatous optic neuropathy
• Glaucomatous visual field loss
• Misclassification
• Surrogate

ACKNOWLEDGMENTS

Financial support: The Netherlands Organization for Health Research and Development (ZonMw) grant 2200.0035, The Hague; Lijf en Leven, Krimpen a/d Lek; MD Fonds, Utrecht. Oogfonds Nederland, Utrecht; Stichting Nederlands Oogheelkundig Onderzoek, Nijmegen/Rotterdam; Swart van Essen, Rotterdam; Netherlands Organisation for Scientific Research (NWO), The Hague; Bevordering van Volkskracht, Rotterdam; Blindenhulp, The Hague; Landelijke Stichting voor Blinden en Slechtzienden (LSBS), Utrecht; Rotterdamse Vereniging voor Blindenbelangen, Rotterdam; OOG, The Hague; Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (ANVVB), Doorn; Laméris Ootech BV, Nieuwegein; Topcon Europe BV, Capelle aan de IJssel, all in the Netherlands, and Heidelberg Engineering, Dossenheim, Germany.

The sponsors or funding organizations had no role in the design, conduct, analysis or publication of this research.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.