title: 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: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The optimal cup-disc ratio cut-off point for risk-factor analysis is close to the commonly used 97.5th percentile.
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Wishal D
authors.initials: WD
authors.lastname: Ramdas
authors.forename: Dimitris
authors.initials: D
authors.lastname: Rizopoulos
authors.forename: Roger C W
authors.initials: RC
authors.lastname: Wolfs
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.forename: Nomdo M
authors.initials: NM
authors.lastname: Jansonius
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005901:Glaucoma / Q000175:diagnosis* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009798:Ocular Hypertension / Q000175:diagnosis; D009898:Optic Disk / Q000473:pathology*; D009901:Optic Nerve Diseases / Q000175:diagnosis* / Q000453:epidemiology; D012016:Reference Values; D018570:Risk Assessment; D012307:Risk Factors; D041622:Tomography, Optical; D014794:Visual Fields