Using Small Samples to Evaluate Normative Reference Ranges for Retinal Imaging Measures

SIGNIFICANCE: Retinal nerve fiber layer (RNFL) deviation maps often incorrectly score healthy eyes as having wedge defects. This study shows how to identify such problems early in the development of normative databases. PURPOSE: After reference values are embedded in devices, clinicians and researchers often learn about issues that cause false-positive rates in healthy eyes. Here we show a way to detect and address such issues early on. METHODS: The thickness of the RNFL was measured for both eyes of 60 healthy younger adults aged 20 to 31 years and one eye each of 30 healthy older adults aged 54 to 82 years. Deviation maps were developed from the left eyes of the first 30 younger adults, and between-subject variability in the shape of the RNFL was assessed. This was repeated in their right eyes, in the second group of younger adults and in the older adults. RESULTS: For the first group of 30 healthy young adults, between-subject variability in the location of the region of greatest thickness meant that 58% of the pixels below the fifth percentile in the left eyes were from four people whose deviation maps had wedge-shaped patterns, as did the deviation maps for the nine right eyes with 87% of the pixels below the fifth percentile. Wedge patterns were also seen in deviation maps for 8 left eyes and 11 right eyes of the second group of young adults and for 9 eyes of the older adults. CONCLUSIONS: Evaluation of RNFL thickness maps from 30 young adults was sufficient to determine that between-subject variability in the shape of the RNFL can cause wedge patterns in RNFL deviation maps in many healthy eyes.