Likelihood ratios for glaucoma diagnosis using spectral-domain optical coherence tomography

Abstract

Purpose: To present a methodology for calculating likelihood ratios for glaucoma diagnosis for continuous retinal nerve fiber layer (RNFL) thickness measurements from spectral-domain optical coherence tomography (spectral-domain OCT).

Design: Observational cohort study.

Methods: A total of 262 eyes of 187 patients with glaucoma and 190 eyes of 100 control subjects were included in the study. Subjects were recruited from the Diagnostic Innovations Glaucoma Study. Eyes with preperimetric and perimetric glaucomatous damage were included in the glaucoma group. The control group was composed of healthy eyes with normal visual fields from subjects recruited from the general population. All eyes underwent RNFL imaging with Spectralis spectral-domain OCT. Likelihood ratios for glaucoma diagnosis were estimated for specific global RNFL thickness measurements using a methodology based on estimating the tangents to the receiver operating characteristic (ROC) curve.

Results: Likelihood ratios could be determined for continuous values of average RNFL thickness. Average RNFL thickness values lower than 86 μm were associated with positive likelihood ratios (ie, likelihood ratios greater than 1), whereas RNFL thickness values higher than 86 μm were associated with negative likelihood ratios (ie, likelihood ratios smaller than 1). A modified Fagan nomogram was provided to assist calculation of posttest probability of disease from the calculated likelihood ratios and pretest probability of disease.

Conclusion: The methodology allowed calculation of likelihood ratios for specific RNFL thickness values. By avoiding arbitrary categorization of test results, it potentially allows for an improved integration of test results into diagnostic clinical decision making.

Trial registration: ClinicalTrials.gov NCT00221897.

Copyright © 2013. Published by Elsevier Inc.

Figures

FIGURE 1

Relationship between likelihood ratios for glaucoma diagnosis and global retinal nerve fiber layer thickness measurements for likelihood ratios values greater than 1, i.e., associated with increased post-test probability of disease.

FIGURE 2

Relationship between likelihood ratios for glaucoma diagnosis and global retinal nerve fiber layer thickness measurements for likelihood ratios values smaller than 1, i.e., associated with decrease in the post-test probability of disease.

FIGURE 3

Relationship between post-test probability of disease for glaucoma diagnosis and retinal nerve fiber layer thicknesses.

FIGURE 4

Relationship between post-test probability of disease for glaucoma diagnosis and pretest probability of disease.

FIGURE 5

Modified Fagan’s nomogram for calculation of the post-test probability of glaucoma according to the pretest probability of glaucoma and continuous values of global retinal nerve fiber layer thickness.

FIGURE 6

Examples of eyes included in the study illustrating the benefits of incorporating diagnostic likelihood ratios for continuous test results in the diagnostic process. Based on the medical history, clinical examination, intraocular pressure and visual field exam, the eye at the top was considered to have a pretest probability of 40%. The spectral-domain OCT measured a RNFL thickness of 67μm. By applying the modified Fagan nomogram we can see that the post-test probability increased to 97%. Conversely, the eye at the bottom was considered to have a pretest probability of 60%. The spectral-domain OCT measured a RNFL thickness of 104μm. By applying the modified Fagan nomogram the post-test probability decreased considerably to 18%.