Evidence map›Paper›PMID 25633665›Full record

ArticleDiabetes care2015

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 and 7 more

Registry-linked trialOpen access · greenAbstract readEvaluation StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes care, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02423434 (Multinational Collaborative Evaluation of Corneal Confocal Microscopy as a Surrogate Endpoint for the Identification and Prediction of Diabetic Neuropathy in Type 1 Diabetes), which is not on this map. Cited by 114 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 1 pooled it
16.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02423434 completednot on this map

Multinational Collaborative Evaluation of Corneal Confocal Microscopy as a Surrogate Endpoint for the Identification and Prediction of Diabetic Neuropathy in Type 1 Diabetes

TypeobservationalSponsorSamuel Lunenfeld Research Institute, Mount Sinai HospitalRan2014 to 2018Enrolled624ConditionsDiabetic Polyneuropathy, Diabetes Mellitus, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2ArmsExposure: Corneal nerve fibre morphology by the CCM Procedure
3 · Its place in the literature

Who cites it

114 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Observational
  12. Article
  13. Observational
  14. The Impact of Aging and Sex on Corneal Nerve Density and Function.Investigative ophthalmology & visual science · 2026
    Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

54 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 7 institutions in 5 countries.

Mitra TavakoliCentre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, U.K.
Maryam FerdousiCentre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, U.K.
Ioannis N PetropoulosCentre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, U.K.
Julie MorrisMedical Statistics Unit, University of Manchester and University Hospital of South Manchester, Manchester, U.K.
Nicola PritchardInstitute of Health Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
Andrey ZhivovDepartment of Ophthalmology, University of Rostock, Rostock, Germany.
Dan ZieglerInstitute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany Department of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany.
Danièle PacaudAlberta Children's Hospital, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.
Kenneth RomanchukAlberta Children's Hospital, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.
Bruce A PerkinsDivision of Endocrinology, Leadership Sinai Centre for Diabetes, University of Toronto, Toronto, Canada.
Leif E LovblomDivision of Endocrinology, Leadership Sinai Centre for Diabetes, University of Toronto, Toronto, Canada.
Vera BrilDivision of Neurology, University Health Network, University of Toronto, Toronto, Canada.
J Robinson SingletonDepartment of Neurology, University of Utah, Salt Lake City, UT.
Gordon SmithDepartment of Neurology, University of Utah, Salt Lake City, UT.
Andrew J M BoultonCentre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, U.K.
Nathan EfronInstitute of Health Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
Rayaz A MalikCentre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, U.K. Weill Cornell Medical College in Qatar, Ar Rayyān, Qatar rayaz.a.malik@man.ac.uk.
University of Toronto · CAQueensland University of Technology · AUUniversity of Calgary · CAUniversity of Utah · USDüsseldorf University Hospital · DEUniversity of Rostock · DEWeill Cornell Medical College in Qatar · QA

Funding

The Utah Diabetic Neuropathy StudyR01DK064814 · NIDDK · UNIVERSITY OF UTAH · PI SINGLETON, JOHN ROBINSON, SMITH, A. GORDON · 2004 to 2019
$7.8M
NIDDK NIH HHS R01 DK064814NIDDK NIH HHS R01-DK064814PHS HHS 1ULTR001067PHS HHS R1-05991Wellcome Trust
6 · The paper itself

Abstract

objectiveCorneal 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

methodsA 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.

resultsThere was a significant linear age-dependent decrease in CNFD (-0.164 no./mm(2) per year for men, P < 0.01, and -0.161 no./mm(2) per year for women, P < 0.01). There was no change with age in CNBD (0.192 no./mm(2) per year for men, P = 0.26, and -0.050 no./mm(2) per year for women, P = 0.78). CNFL decreased in men (-0.045 mm/mm(2) per year, P = 0.07) and women (-0.060 mm/mm(2) 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.

conclusionsThis 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.

Indexed as

AdolescentAdultAgedAged, 80 and overAge FactorsCase-Control StudiesChildCorneaDiabetic NeuropathiesFemaleHealthy VolunteersHumansLinear ModelsMaleMicroscopy, ConfocalMiddle Aged

Identifiers

PMID25633665
PMCPMC4407754
OpenAlexW2143048304

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.