An Analysis of Normal Variability in OCT Retinal Nerve Fiber Layer Thickness Provides a Better Understanding of False Positives

Abstract

Purpose:: To better understand the conditions under which optical coherence tomography (OCT) results in a false positive (i.e. an eye with normal vision being classified as abnormal), normal variations in retinal nerve fiber layer (RNFL) thickness were examined.

Methods:: Fifty individuals with normal vision and refractive errors between ±6D were tested with the fast RNFL scan protocol of the OCT3 (Zeiss Meditech) and their 256 point RNFL profiles were exported for analysis. To assess the consequences of "true" intra-subject variability, steps were taken to minimize measurement error, including repeat testing on a second day. Care was taken to center the optic disc within the scanning circle. The positions and peak amplitudes of the temporal and nasal-most peaks of the RNFL profile were measured. The positions of the peaks were measured on the 256-point scale used by the OCT3 and then converted to degrees. 0 degrees represents the temporal-most location [9 o’clock (OD)] and 180 degrees the nasal-most location [3 o’clock (OD)]. A hemifield was defined as abnormal on the OCT if one of the 5 sectors (sectors at 3 and 9 o’clock were excluded) was at < 1% (red) or two sectors were at < 5% (yellow). This criterion (2Y1R) has high sensitivity and specificity.¹

Results:: On average, the amplitude of the superior (inferior) RNFL peak was 153.5 ± 18.5 (160.3 ± 21.0) µm. They were located at 36.9 ± 5.6° (145.3 ± 5.7°). However, there was a wide variation in the shape of the individual RNFL profiles. For example, the position of the superior (inferior) peaks ranged over 27.7° (36.3°) and the range of the amplitudes spanned a factor of 1.8 (1.9). Not surprisingly, the 4 abnormal hemifields, on average, had smaller peak amplitudes. However, only 1 of the 4 amplitudes fell outside the 95% confidence intervals. More remarkably, the positions of the peaks for all 4 fell on, or outside, the 95% confidence limit. In general, the RNFL profiles of the two eyes were extremely similar.

Conclusions:: RNFL thickness profiles with peaks located at the extremes of the normal range may be classified as abnormal. If a patient’s RNFL profile has peaks located near the extremes of the normal range, and if the profiles of the two eyes are the same, a false positive should be suspected. 1. Hood et al ARVO 2006

Keywords: nerve fiber layer • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)