Normative values for corneal nerve morphology assessed using corneal confocal microscopy

A multinational normative data set

Mitra Tavakoli, Maryam Ferdousi, Ioannis N. Petropoulos, Julie Morris, Nicola Pritchard, Andrey Zhivov, Dan Ziegler, Danièle Pacaud, Kenneth Romanchuk, Bruce A. Perkins, Leif E. Lovblom, Vera Bril, J. Robinson Singleton, Gordon Smith, Andrew J M Boulton, Nathan Efron, Rayaz Malik

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

OBJECTIVE: Corneal confocal microscopy is a novel diagnostic technique for the detection of nerve damage and repair in a range of peripheral neuropathies, in particular diabetic neuropathy. Normative reference values are required to enable clinical translation and wider use of this technique. We have therefore undertaken a multicenter collaboration to provide worldwide age-adjusted normative values of corneal nerve fiber parameters. RESEARCH DESIGN AND METHODS: A total of 1,965 corneal nerve images from 343 healthy volunteers were pooled from six clinical academic centers. All subjects underwent examination with the Heidelberg Retina Tomograph corneal confocal microscope. Images of the central corneal subbasal nerve plexus were acquired by each center using a standard protocol and analyzed by three trained examiners using manual tracing and semiautomated software (CCMetrics). Age trends were established using simple linear regression, and normative corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) reference values were calculated using quantile regression analysis. RESULTS: There was a significant linear age-dependent decrease in CNFD (-0.164 no./mm2 per year for men, P < 0.01, and -0.161 no./mm2 per year for women, P < 0.01). There was no change with age in CNBD (0.192 no./mm2 per year for men, P = 0.26, and -0.050 no./mm2 per year for women, P = 0.78). CNFL decreased in men (-0.045 mm/mm2 per year, P = 0.07) and women (-0.060 mm/mm2 per year, P = 0.02). CNFT increased with age in men (0.044 per year, P < 0.01) and women (0.046 per year, P < 0.01). Height, weight, and BMI did not influence the 5th percentile normative values for any corneal nerve parameter. CONCLUSIONS: This study provides robust worldwide normative reference values for corneal nerve parameters to be used in research and clinical practice in the study of diabetic and other peripheral neuropathies.

Original languageEnglish
Pages (from-to)838-843
Number of pages6
JournalDiabetes Care
Volume38
Issue number5
DOIs
Publication statusPublished - 1 May 2015

Fingerprint

Nerve Fibers
Confocal Microscopy
Reference Values
Peripheral Nervous System Diseases
Datasets
Diabetic Neuropathies
Retina
Linear Models
Healthy Volunteers
Research Design
Software
Regression Analysis
Weights and Measures
Research

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing
  • Medicine(all)

Cite this

Normative values for corneal nerve morphology assessed using corneal confocal microscopy : A multinational normative data set. / Tavakoli, Mitra; Ferdousi, Maryam; Petropoulos, Ioannis N.; Morris, Julie; Pritchard, Nicola; Zhivov, Andrey; Ziegler, Dan; Pacaud, Danièle; Romanchuk, Kenneth; Perkins, Bruce A.; Lovblom, Leif E.; Bril, Vera; Robinson Singleton, J.; Smith, Gordon; Boulton, Andrew J M; Efron, Nathan; Malik, Rayaz.

In: Diabetes Care, Vol. 38, No. 5, 01.05.2015, p. 838-843.

Research output: Contribution to journalArticle

Tavakoli, M, Ferdousi, M, Petropoulos, IN, Morris, J, Pritchard, N, Zhivov, A, Ziegler, D, Pacaud, D, Romanchuk, K, Perkins, BA, Lovblom, LE, Bril, V, Robinson Singleton, J, Smith, G, Boulton, AJM, Efron, N & Malik, R 2015, 'Normative values for corneal nerve morphology assessed using corneal confocal microscopy: A multinational normative data set', Diabetes Care, vol. 38, no. 5, pp. 838-843. https://doi.org/10.2337/dc14-2311
Tavakoli, Mitra ; Ferdousi, Maryam ; Petropoulos, Ioannis N. ; Morris, Julie ; Pritchard, Nicola ; Zhivov, Andrey ; Ziegler, Dan ; Pacaud, Danièle ; Romanchuk, Kenneth ; Perkins, Bruce A. ; Lovblom, Leif E. ; Bril, Vera ; Robinson Singleton, J. ; Smith, Gordon ; Boulton, Andrew J M ; Efron, Nathan ; Malik, Rayaz. / Normative values for corneal nerve morphology assessed using corneal confocal microscopy : A multinational normative data set. In: Diabetes Care. 2015 ; Vol. 38, No. 5. pp. 838-843.
@article{5429d534d6b04c29912f0517cca92501,
title = "Normative values for corneal nerve morphology assessed using corneal confocal microscopy: A multinational normative data set",
abstract = "OBJECTIVE: Corneal confocal microscopy is a novel diagnostic technique for the detection of nerve damage and repair in a range of peripheral neuropathies, in particular diabetic neuropathy. Normative reference values are required to enable clinical translation and wider use of this technique. We have therefore undertaken a multicenter collaboration to provide worldwide age-adjusted normative values of corneal nerve fiber parameters. RESEARCH DESIGN AND METHODS: A total of 1,965 corneal nerve images from 343 healthy volunteers were pooled from six clinical academic centers. All subjects underwent examination with the Heidelberg Retina Tomograph corneal confocal microscope. Images of the central corneal subbasal nerve plexus were acquired by each center using a standard protocol and analyzed by three trained examiners using manual tracing and semiautomated software (CCMetrics). Age trends were established using simple linear regression, and normative corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) reference values were calculated using quantile regression analysis. RESULTS: There was a significant linear age-dependent decrease in CNFD (-0.164 no./mm2 per year for men, P < 0.01, and -0.161 no./mm2 per year for women, P < 0.01). There was no change with age in CNBD (0.192 no./mm2 per year for men, P = 0.26, and -0.050 no./mm2 per year for women, P = 0.78). CNFL decreased in men (-0.045 mm/mm2 per year, P = 0.07) and women (-0.060 mm/mm2 per year, P = 0.02). CNFT increased with age in men (0.044 per year, P < 0.01) and women (0.046 per year, P < 0.01). Height, weight, and BMI did not influence the 5th percentile normative values for any corneal nerve parameter. CONCLUSIONS: This study provides robust worldwide normative reference values for corneal nerve parameters to be used in research and clinical practice in the study of diabetic and other peripheral neuropathies.",
author = "Mitra Tavakoli and Maryam Ferdousi and Petropoulos, {Ioannis N.} and Julie Morris and Nicola Pritchard and Andrey Zhivov and Dan Ziegler and Dani{\`e}le Pacaud and Kenneth Romanchuk and Perkins, {Bruce A.} and Lovblom, {Leif E.} and Vera Bril and {Robinson Singleton}, J. and Gordon Smith and Boulton, {Andrew J M} and Nathan Efron and Rayaz Malik",
year = "2015",
month = "5",
day = "1",
doi = "10.2337/dc14-2311",
language = "English",
volume = "38",
pages = "838--843",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "5",

}

TY - JOUR

T1 - Normative values for corneal nerve morphology assessed using corneal confocal microscopy

T2 - A multinational normative data set

AU - Tavakoli, Mitra

AU - Ferdousi, Maryam

AU - Petropoulos, Ioannis N.

AU - Morris, Julie

AU - Pritchard, Nicola

AU - Zhivov, Andrey

AU - Ziegler, Dan

AU - Pacaud, Danièle

AU - Romanchuk, Kenneth

AU - Perkins, Bruce A.

AU - Lovblom, Leif E.

AU - Bril, Vera

AU - Robinson Singleton, J.

AU - Smith, Gordon

AU - Boulton, Andrew J M

AU - Efron, Nathan

AU - Malik, Rayaz

PY - 2015/5/1

Y1 - 2015/5/1

N2 - OBJECTIVE: Corneal confocal microscopy is a novel diagnostic technique for the detection of nerve damage and repair in a range of peripheral neuropathies, in particular diabetic neuropathy. Normative reference values are required to enable clinical translation and wider use of this technique. We have therefore undertaken a multicenter collaboration to provide worldwide age-adjusted normative values of corneal nerve fiber parameters. RESEARCH DESIGN AND METHODS: A total of 1,965 corneal nerve images from 343 healthy volunteers were pooled from six clinical academic centers. All subjects underwent examination with the Heidelberg Retina Tomograph corneal confocal microscope. Images of the central corneal subbasal nerve plexus were acquired by each center using a standard protocol and analyzed by three trained examiners using manual tracing and semiautomated software (CCMetrics). Age trends were established using simple linear regression, and normative corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) reference values were calculated using quantile regression analysis. RESULTS: There was a significant linear age-dependent decrease in CNFD (-0.164 no./mm2 per year for men, P < 0.01, and -0.161 no./mm2 per year for women, P < 0.01). There was no change with age in CNBD (0.192 no./mm2 per year for men, P = 0.26, and -0.050 no./mm2 per year for women, P = 0.78). CNFL decreased in men (-0.045 mm/mm2 per year, P = 0.07) and women (-0.060 mm/mm2 per year, P = 0.02). CNFT increased with age in men (0.044 per year, P < 0.01) and women (0.046 per year, P < 0.01). Height, weight, and BMI did not influence the 5th percentile normative values for any corneal nerve parameter. CONCLUSIONS: This study provides robust worldwide normative reference values for corneal nerve parameters to be used in research and clinical practice in the study of diabetic and other peripheral neuropathies.

AB - OBJECTIVE: Corneal confocal microscopy is a novel diagnostic technique for the detection of nerve damage and repair in a range of peripheral neuropathies, in particular diabetic neuropathy. Normative reference values are required to enable clinical translation and wider use of this technique. We have therefore undertaken a multicenter collaboration to provide worldwide age-adjusted normative values of corneal nerve fiber parameters. RESEARCH DESIGN AND METHODS: A total of 1,965 corneal nerve images from 343 healthy volunteers were pooled from six clinical academic centers. All subjects underwent examination with the Heidelberg Retina Tomograph corneal confocal microscope. Images of the central corneal subbasal nerve plexus were acquired by each center using a standard protocol and analyzed by three trained examiners using manual tracing and semiautomated software (CCMetrics). Age trends were established using simple linear regression, and normative corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) reference values were calculated using quantile regression analysis. RESULTS: There was a significant linear age-dependent decrease in CNFD (-0.164 no./mm2 per year for men, P < 0.01, and -0.161 no./mm2 per year for women, P < 0.01). There was no change with age in CNBD (0.192 no./mm2 per year for men, P = 0.26, and -0.050 no./mm2 per year for women, P = 0.78). CNFL decreased in men (-0.045 mm/mm2 per year, P = 0.07) and women (-0.060 mm/mm2 per year, P = 0.02). CNFT increased with age in men (0.044 per year, P < 0.01) and women (0.046 per year, P < 0.01). Height, weight, and BMI did not influence the 5th percentile normative values for any corneal nerve parameter. CONCLUSIONS: This study provides robust worldwide normative reference values for corneal nerve parameters to be used in research and clinical practice in the study of diabetic and other peripheral neuropathies.

UR - http://www.scopus.com/inward/record.url?scp=84933674859&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84933674859&partnerID=8YFLogxK

U2 - 10.2337/dc14-2311

DO - 10.2337/dc14-2311

M3 - Article

VL - 38

SP - 838

EP - 843

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 5

ER -