Natural history of corneal nerve morphology in mild neuropathy associated with type 1 diabetes

Development of a potential measure of diabetic peripheral neuropathy

Cirous Dehghani, Nicola Pritchard, Katie Edwards, Dimitrios Vagenas, Anthony W. Russell, Rayaz Malik, Nathan Efron

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Purpose: To investigate longitudinal changes of subbasal nerve plexus (SNP) morphology and its relationship with conventional measures of neuropathy in individuals with diabetes.

Methods: A cohort of 147 individuals with type 1 diabetes and 60 age-balanced controls underwent detailed assessment of clinical and metabolic factors, neurologic deficits, quantitative sensory testing, nerve conduction studies, and corneal confocal microscopy at baseline and four subsequent annual visits. The SNP parameters included corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL), and were quantified using a fully automated algorithm. Linear mixed models were fitted to examine the changes in corneal nerve parameters over time.

Results: At baseline, 27% of the participants had mild diabetic neuropathy. All SNP parameters were significantly lower in the neuropathy group compared with controls (P < 0.05). Overall, 89% of participants examined at baseline also completed the final visit. There was no clinically significant change to health and metabolic parameters and neuropathy measures from baseline to the final visit. Linear mixed model revealed a significant linear decline of CNFD (annual change rate, −0.9 nerve/mm2, P = 0.01) in the neuropathy group compared with controls, which was associated with age (β = −0.06, P = 0.04) and duration of diabetes (β = −0.08, P = 0.03). In the neuropathy group, absolute changes of CNBD and CNFL showed moderate correlations with peroneal conduction velocity and cold sensation threshold, respectively (r, 0.38 and 0.40, P < 0.05).

Conclusions: This study demonstrates dynamic small fiber damage at the SNP, thus providing justification for our ongoing efforts to establish corneal nerve morphology as an appropriate adjunct to conventional measures of diabetic peripheral neuropathy.

Original languageEnglish
Pages (from-to)7982-7990
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number12
DOIs
Publication statusPublished - 18 Nov 2014
Externally publishedYes

Fingerprint

Diabetic Neuropathies
Peripheral Nervous System Diseases
Natural History
Type 1 Diabetes Mellitus
Nerve Fibers
Linear Models
Neural Conduction
Neurologic Manifestations
Confocal Microscopy
Health

Keywords

  • Corneal confocal microscopy
  • Diabetes
  • Natural history

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Natural history of corneal nerve morphology in mild neuropathy associated with type 1 diabetes : Development of a potential measure of diabetic peripheral neuropathy. / Dehghani, Cirous; Pritchard, Nicola; Edwards, Katie; Vagenas, Dimitrios; Russell, Anthony W.; Malik, Rayaz; Efron, Nathan.

In: Investigative Ophthalmology and Visual Science, Vol. 55, No. 12, 18.11.2014, p. 7982-7990.

Research output: Contribution to journalArticle

Dehghani, Cirous ; Pritchard, Nicola ; Edwards, Katie ; Vagenas, Dimitrios ; Russell, Anthony W. ; Malik, Rayaz ; Efron, Nathan. / Natural history of corneal nerve morphology in mild neuropathy associated with type 1 diabetes : Development of a potential measure of diabetic peripheral neuropathy. In: Investigative Ophthalmology and Visual Science. 2014 ; Vol. 55, No. 12. pp. 7982-7990.
@article{7d140d68b66e45849793188e0047da19,
title = "Natural history of corneal nerve morphology in mild neuropathy associated with type 1 diabetes: Development of a potential measure of diabetic peripheral neuropathy",
abstract = "Purpose: To investigate longitudinal changes of subbasal nerve plexus (SNP) morphology and its relationship with conventional measures of neuropathy in individuals with diabetes.Methods: A cohort of 147 individuals with type 1 diabetes and 60 age-balanced controls underwent detailed assessment of clinical and metabolic factors, neurologic deficits, quantitative sensory testing, nerve conduction studies, and corneal confocal microscopy at baseline and four subsequent annual visits. The SNP parameters included corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL), and were quantified using a fully automated algorithm. Linear mixed models were fitted to examine the changes in corneal nerve parameters over time.Results: At baseline, 27{\%} of the participants had mild diabetic neuropathy. All SNP parameters were significantly lower in the neuropathy group compared with controls (P < 0.05). Overall, 89{\%} of participants examined at baseline also completed the final visit. There was no clinically significant change to health and metabolic parameters and neuropathy measures from baseline to the final visit. Linear mixed model revealed a significant linear decline of CNFD (annual change rate, −0.9 nerve/mm2, P = 0.01) in the neuropathy group compared with controls, which was associated with age (β = −0.06, P = 0.04) and duration of diabetes (β = −0.08, P = 0.03). In the neuropathy group, absolute changes of CNBD and CNFL showed moderate correlations with peroneal conduction velocity and cold sensation threshold, respectively (r, 0.38 and 0.40, P < 0.05).Conclusions: This study demonstrates dynamic small fiber damage at the SNP, thus providing justification for our ongoing efforts to establish corneal nerve morphology as an appropriate adjunct to conventional measures of diabetic peripheral neuropathy.",
keywords = "Corneal confocal microscopy, Diabetes, Natural history",
author = "Cirous Dehghani and Nicola Pritchard and Katie Edwards and Dimitrios Vagenas and Russell, {Anthony W.} and Rayaz Malik and Nathan Efron",
year = "2014",
month = "11",
day = "18",
doi = "10.1167/iovs.14-15605",
language = "English",
volume = "55",
pages = "7982--7990",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "12",

}

TY - JOUR

T1 - Natural history of corneal nerve morphology in mild neuropathy associated with type 1 diabetes

T2 - Development of a potential measure of diabetic peripheral neuropathy

AU - Dehghani, Cirous

AU - Pritchard, Nicola

AU - Edwards, Katie

AU - Vagenas, Dimitrios

AU - Russell, Anthony W.

AU - Malik, Rayaz

AU - Efron, Nathan

PY - 2014/11/18

Y1 - 2014/11/18

N2 - Purpose: To investigate longitudinal changes of subbasal nerve plexus (SNP) morphology and its relationship with conventional measures of neuropathy in individuals with diabetes.Methods: A cohort of 147 individuals with type 1 diabetes and 60 age-balanced controls underwent detailed assessment of clinical and metabolic factors, neurologic deficits, quantitative sensory testing, nerve conduction studies, and corneal confocal microscopy at baseline and four subsequent annual visits. The SNP parameters included corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL), and were quantified using a fully automated algorithm. Linear mixed models were fitted to examine the changes in corneal nerve parameters over time.Results: At baseline, 27% of the participants had mild diabetic neuropathy. All SNP parameters were significantly lower in the neuropathy group compared with controls (P < 0.05). Overall, 89% of participants examined at baseline also completed the final visit. There was no clinically significant change to health and metabolic parameters and neuropathy measures from baseline to the final visit. Linear mixed model revealed a significant linear decline of CNFD (annual change rate, −0.9 nerve/mm2, P = 0.01) in the neuropathy group compared with controls, which was associated with age (β = −0.06, P = 0.04) and duration of diabetes (β = −0.08, P = 0.03). In the neuropathy group, absolute changes of CNBD and CNFL showed moderate correlations with peroneal conduction velocity and cold sensation threshold, respectively (r, 0.38 and 0.40, P < 0.05).Conclusions: This study demonstrates dynamic small fiber damage at the SNP, thus providing justification for our ongoing efforts to establish corneal nerve morphology as an appropriate adjunct to conventional measures of diabetic peripheral neuropathy.

AB - Purpose: To investigate longitudinal changes of subbasal nerve plexus (SNP) morphology and its relationship with conventional measures of neuropathy in individuals with diabetes.Methods: A cohort of 147 individuals with type 1 diabetes and 60 age-balanced controls underwent detailed assessment of clinical and metabolic factors, neurologic deficits, quantitative sensory testing, nerve conduction studies, and corneal confocal microscopy at baseline and four subsequent annual visits. The SNP parameters included corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL), and were quantified using a fully automated algorithm. Linear mixed models were fitted to examine the changes in corneal nerve parameters over time.Results: At baseline, 27% of the participants had mild diabetic neuropathy. All SNP parameters were significantly lower in the neuropathy group compared with controls (P < 0.05). Overall, 89% of participants examined at baseline also completed the final visit. There was no clinically significant change to health and metabolic parameters and neuropathy measures from baseline to the final visit. Linear mixed model revealed a significant linear decline of CNFD (annual change rate, −0.9 nerve/mm2, P = 0.01) in the neuropathy group compared with controls, which was associated with age (β = −0.06, P = 0.04) and duration of diabetes (β = −0.08, P = 0.03). In the neuropathy group, absolute changes of CNBD and CNFL showed moderate correlations with peroneal conduction velocity and cold sensation threshold, respectively (r, 0.38 and 0.40, P < 0.05).Conclusions: This study demonstrates dynamic small fiber damage at the SNP, thus providing justification for our ongoing efforts to establish corneal nerve morphology as an appropriate adjunct to conventional measures of diabetic peripheral neuropathy.

KW - Corneal confocal microscopy

KW - Diabetes

KW - Natural history

UR - http://www.scopus.com/inward/record.url?scp=84916899007&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84916899007&partnerID=8YFLogxK

U2 - 10.1167/iovs.14-15605

DO - 10.1167/iovs.14-15605

M3 - Article

VL - 55

SP - 7982

EP - 7990

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 12

ER -