Reference ranges for clinical electrophysiology of vision

Abstract

Introduction Establishing robust reference intervals for clinical procedures has received much attention from international clinical laboratories, with approved guidelines. Physiological measurement laboratories have given this topic less attention; however, most of the principles are transferable. Methods Herein, we summarise those principles and expand them to cover bilateral measurements and one-tailed reference intervals, which are common issues for those interpreting clinical visual electrophysiology tests such as electroretinograms (ERGs), visual evoked potentials (VEPs) and electrooculograms (EOGs). Results The gold standard process of establishing and defining reference intervals, which are adequately reliable, entails collecting data from a minimum of 120 suitable reference individuals for each partition (e.g. sex, age) and defining limits with nonparametric methods. Parametric techniques may be used under some conditions. A brief outline of methods for defining reference limits from patient data (indirect sampling) is given. Reference intervals established elsewhere, or with older protocols, can be transferred or verified with as few as 40 and 20 suitable reference individuals, respectively. Consideration is given to small numbers of reference subjects, interpretation of serial measurements using subject-based reference values, multidimensional reference regions and age-dependent reference values. Bilateral measurements, despite their correlation, can be used to improve reference intervals although additional care is required in computing the confidence in the reference interval or the reference interval itself when bilateral measurements are only available from some of subjects. Discussion Good quality reference limits minimise false-positive and false-negative results, thereby maximising the clinical utility and patient benefit. Quality indicators include using appropriately sized reference datasets with appropriate numerical handling for reporting; using subject-based reference limits where appropriate; and limiting tests for each patient to only those which are clinically indicated, independent and highly discriminating.

Mydriasis-Free Flicker Electroretinograms in 204 Healthy Children Aged 0–18 Years: Reference Data From Two Cohorts

“…Therefore, all the data can be combined to compute percentiles which can then be added back to the age-dependent fits. 17 The percentiles needed for 95% reference intervals (both 1 and 2 tailed) are shown in Figure 1 . The amounts to be added to reach a certain percentile are shown in Table 1 .…”

“…Nevertheless, the differences are sufficiently small compared to the 95% reference interval that partitioning is not required. 17 …”

“…Analyses were performed using Mathematica Version 12.3 (Wolfram Research, Champaign, IL, USA). Following Davis and Hamilton, 17 data from both eyes are used for the analysis. The results from one eye was missing in 38 individuals; these results were duplicated so that each subject had 2 results.…”

“…The residuals did not show an age dependence, so percentiles were computed on the residuals, which are then added back to the fits to form age-dependent reference intervals. 17 The results were considered statistically significant when the P value was less than 0.05.…”

Comprehensive visual electrophysiological measurements discover crucial changes caused by alcohol addiction in humans: Clinical values in early prevention of alcoholic vision decline

“…In cases when subjects have single-eye data, we duplicated the values of the available eye so that all subjects have a pair of results. This strategy has considered the correlation between eyes from the same subjects, can achieve more accurate estimations, and is proved better than using only one eye's data by our study and also by literature (Davis and Hamilton, 2021). All statistical analysis and data visualization were performed using R software.…”