Population-based evaluation of retinal nerve fiber layer, retinal ganglion cell layer, and inner plexiform layer as a diagnostic tool for glaucoma

Abstract

Purpose: We determined the glaucoma screening performance of regional optical coherence tomography (OCT) layer thickness measurements in the peripapillary and macular region, in a population-based setting.

Methods: Subjects (n = 1224) in the Rotterdam Study underwent visual field testing (Humphrey Field Analyzer) and OCT of the macula and optic nerve head (Topcon 3-D OCT-1000). We determined the mean thicknesses of the retinal nerve fiber layer (RNFL), retinal ganglion cell layer (RGCL), and inner plexiform layer for regions-of-interest; thus, defining a series of OCT parameters, using the Iowa Reference Algorithms. Reference standard was the presence of glaucomatous visual field loss (GVFL); controls were subjects without GVFL, an intraocular pressure (IOP) of 21 mm Hg or less, and no positive family history for glaucoma. We calculated the area under the receiver operating characteristics curve (AUCs) and the sensitivity at 97.5% specificity for each parameter.

Results: After excluding 23 subjects with an IOP > 21 mm Hg and 73 subjects with a positive family history for glaucoma, there were 1087 controls and 41 glaucoma cases. Mean RGCL thickness in the inferior half of the macular region showed the highest AUC (0.85; 95% confidence interval [CI] 0.77-0.92) and sensitivity (53.7%; 95% CI, 38.7-68.0%). The mean thickness of the peripapillary RNFL had an AUC of 0.77 (95% CI, 0.69-0.85) and a sensitivity of 24.4% (95% CI, 13.7-39.5%).

Conclusions: Macular RGCL loss is at least as common as peripapillary RNFL abnormalities in population-based glaucoma cases. Screening for glaucoma using OCT-derived regional thickness identifies approximately half of those cases of glaucoma as diagnosed by perimetry.

Keywords: Iowa Reference Algorithms; OCT; population-based evaluation; retinal thickness measurement.

Figure 1

Schematic overview of the area of the macular scan (left square) and ONH scan (right square).

Figure 2

Division of macular scan region in 11 (A) and 4 (B) color-coded subregions, based on the nerve fiber bundle trajectories as described by Jansonius et al.,^, and the MVZ (C) as described by Hood et al. Dark line represents the border between the superior and inferior part of the scan. Division of peripapillary region in 9 color-coded segments ([D]; *denotes segments that are replaced by macular subregions in the combined variables as described in Table 1).

Figure 3

Scatterplot of mean deviation versus pattern SD for the 41 cases with GVFL. Green dots represent the cases (n = 22) correctly classified by the mean RGCL thickness in the inferior half of the macular region (true-positives). Blue dots represent the false-negative cases (n = 19).

Figure 4

Scatterplot of the mean RGCL thickness in the inferior half of the macular scan versus the mean sensitivity of the eight superiorly located central test locations of the 24-2 grid for the 41 cases with GVFL.

Figure 5

Mean superior macular thickness versus mean inferior macular thickness for the RGCL, for cases (green) and controls (blue).