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.2021 Oct;143(2):155-170.
doi: 10.1007/s10633-021-09831-1. Epub 2021 Apr 21.

Reference ranges for clinical electrophysiology of vision

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Reference ranges for clinical electrophysiology of vision

C Quentin Davis et al. Doc Ophthalmol.2021 Oct.

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.

Keywords: EOG; ERG; ISCEV standard; Normative data; Reference data; Reference interval; Reference limit; VEP.

© 2021. The Author(s).

PubMed Disclaimer

Conflict of interest statement

Quentin Davis is an employee of LKC Technologies, Gaithersburg, Maryland, which manufactures electrophysiology devices that can utilize the subject matter of this article. Ruth Hamilton has no conflicts of interest.

Figures

Fig. 1
Fig. 1
Illustration of terms. Upper panel: example of the distribution of reference values from the reference population shown as a probability density function (idealised data, demonstrated herein with a gamma distribution. The gamma distribution is one of many probability distributions in an exponential family; others include the normal (Gaussian), log-normal and Poisson distributions. It was selected to illustrate a skewed distribution as well as the issues associated with having a mismatch between a fitted model and the underlying data in parametric methods). The reference interval spans from the lower to the upper reference limit and encloses the middle 95% of the distribution. Lower panel: histogram of 120 random measurements sampled from the distribution in the upper panel, forming the reference distribution. The reference intervals and reference limits are derived from sample measurements such as these, along with estimates of the uncertainties of those limits
Fig. 2
Fig. 2
Percentage error in Eq. 2 relative to the non-central Student’s T distribution of the Lawless interval, as a function of number of data points n. Equation 2 provides the confidence intervals for the upper and lower reference limits. All four confidence interval points are shown, although results overlap. Error between Eq. 2 and the non-central Student’s T distribution falls as 1/n
Fig. 3
Fig. 3
Illustration of nonparametric(a, b) and parametric(c, d) reference interval estimates with precision estimates (90% CI). Data are from Fig. 1. Black vertical lines: true reference limits of the underlying population calculated exactly by integrating the probability density function of the continuous gamma distribution used as the source for the sampled data. Dots: sampled data from underlying population. Red vertical lines: reference limits estimated from sample data using the different methods. Grey boxes: 90% CIs of estimated reference limits. For nonparametric estimates(a, b), CIs are wider for the longer (right) tail of the distribution, being 29% of the reference interval in panela, exceeding the 20% goal so that more measurements may be needed. Bootstrapping (1000 × , panelb narrows this CI from 29 to 23% of the reference interval. Estimated limits are close to true limits. Panelc shows parametric (mean ± 1.96 standard deviations) estimates and their CIs. The data do not have a Gaussian distribution (normality test fail,p < 0.05). 90% CIs are incorrectly symmetrical for both reference limits, and inaccurately narrow (13% of the reference interval): the lower CI does not enclose the true reference limit. Paneld shows parametric estimates, performed on log-transformed data, and back-transformed for display. Estimated limits’ 90% CIs enclose the true limits, but the precision of longer (right) tail is 29% of the reference interval, exceeding the 20% goal so that more measurements may be needed. The gaps between true and estimated limits indicate the data distribution deviates somewhat from the assumed log-normal although the statistical test fails to reject the log-normal distribution (p = 0.4). RI: reference interval. CI: confidence interval
Fig. 4
Fig. 4
Uncertainty of reference limits, expressed as the ratio (%) of the 90% confidence interval (CI) of a limit to the whole reference interval (RI), as a function of inter-eye correlation. Three methods for handling correlation between eyes are shown: use one eye per subject (solid lines); use all available eyes as independent samples (dashed lines); and, for subjects with data from only one eye, duplicate the point so that all subjects have data from two eyes, then use all eyes as independent samples (dotted lines). Right panel: all subjects have results from both eyes. Left panel: 75% of subjects have results from both eyes and 25% have results only for one eye. For each correlation coefficient and number of subjects, samples of correlated Gaussian random variables were taken and the lower reference limit was estimated using the nonparametric method. The process was repeated 1,000,000 times for each condition. n: number of subjects
Fig. 5
Fig. 5
Flowcharts outlining simplified processes ofa transference [71] andb verification [2]. RI reference interval, y yes, n no, # number of
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References

    1. Sunderman F. Current concepts of normal values, reference values, and discrimination values in clinical-chemistry. Clin Chem. 1975;21:1873–1877. doi: 10.1093/clinchem/21.13.1873. - DOI - PubMed
    1. Horowitz GL, Clinical and Laboratory Standards Institute (CLSI) (2010) Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline–Third Edition. CLSI document EP28-A3c. Clinical and Laboratory Standards Institute, Wayne, PA
    1. Geffre A, Friedrichs K, Harr K, et al. Reference values: a review. Vet Clin Pathol. 2009;38:288–298. doi: 10.1111/j.1939-165X.2009.00179.x. - DOI - PubMed
    1. Grasbeck R. The evolution of the reference value concept. Clin Chem Lab Med. 2004;42:692–697. doi: 10.1515/CCLM.2004.118. - DOI - PubMed
    1. Siest G, Henny J, Gräsbeck R, et al. The theory of reference values: an unfinished symphony. Clin Chem Lab Med. 2013 doi: 10.1515/cclm-2012-0682. - DOI - PubMed

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