Normative Variability in Retinal Nerve Fiber Layer Thickness: Does It Matter Where the Peaks Are?

Purpose: Retinal nerve fiber layer thickness (RNFLT), a glaucoma biomarker, has a wide normative range affecting its sensitivity and specificity for abnormality detection. The interindividual RNFLT peak location variability contribution to this wide normative range has not been directly evaluated. The purpose of this study is to assess the effect of RNFLT peak normalization (PN) on normative variability. Methods: Circumpapillary RNFLT profiles at 1.7 mm radius from the optic nerve head (ONH) were re-sampled from optical coherence tomography (OCT) volumes (Cirrus HD-OCT, 200 × 200) obtained from one eye of 83 healthy individuals. Fovea-ONH axis (FOA) was calculated from corresponding scanning laser ophthalmoscope images. Supratemporal (ST) and infratemporal (IT) RNFLT peaks of each profile were aligned to respective average peak locations. Normative ranges were calculated by averaging individual profiles before and after PN (with and without FOA to horizontal image axis (HA) alignment). Results: RNFLT-PN resulted in an overall decrease in coefficient of variation (CoV) of the normative range by 4.2% (P = 0.02). CoV was reduced by more than 10% in clock-hours 10 (11.9%), 8 (10.6%), 6 (10.4%) after PN, and 7 (16.3%), 10 (11.4%), and 12 (10.4%) after PN with FOA-HA alignment. RNFLT-PN corrected for abnormality categorization because of peak misalignment in RNFLT profiles of healthy and glaucoma suspect subjects. Conclusions: RNFLT-PN reduces normative variability, especially in the ST and IT regions. Translational Relevance: RNFLT-PN reduces normative variability and improves sectoral abnormality categorization, potentially leading to better sensitivity and specificity of RNFLT measure in glaucoma detection.