Corneal confocal microscopy for identification of diabetic sensorimotor polyneuropathy

a pooled multinational consortium study

Bruce A. Perkins, Leif E. Lovblom, Vera Bril, Daniel Scarr, Ilia Ostrovski, Andrej Orszag, Katie Edwards, Nicola Pritchard, Anthony Russell, Cirous Dehghani, Danièle Pacaud, Kenneth Romanchuk, Jean K. Mah, Maria Jeziorska, Andrew Marshall, Roni M. Shtein, Rodica Pop-Busui, Stephen I. Lentz, Andrew J.M. Boulton, Mitra Tavakoli & 2 others Nathan Efron, Rayaz Malik

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Aims/hypothesis: Small cohort studies raise the hypothesis that corneal nerve abnormalities (including corneal nerve fibre length [CNFL]) are valid non-invasive imaging endpoints for diabetic sensorimotor polyneuropathy (DSP). We aimed to establish concurrent validity and diagnostic thresholds in a large cohort of participants with and without DSP. Methods: Nine hundred and ninety-eight participants from five centres (516 with type 1 diabetes and 482 with type 2 diabetes) underwent CNFL quantification and clinical and electrophysiological examination. AUC and diagnostic thresholds were derived and validated in randomly selected samples using receiver operating characteristic analysis. Sensitivity analyses included latent class models to address the issue of imperfect reference standard. Results: Type 1 and type 2 diabetes subcohorts had mean age of 42 ± 19 and 62 ± 10 years, diabetes duration 21 ± 15 and 12 ± 9 years and DSP prevalence of 31% and 53%, respectively. Derivation AUC for CNFL was 0.77 in type 1 diabetes (p < 0.001) and 0.68 in type 2 diabetes (p < 0.001) and was approximately reproduced in validation sets. The optimal threshold for automated CNFL was 12.5 mm/mm2 in type 1 diabetes and 12.3 mm/mm2 in type 2 diabetes. In the total cohort, a lower threshold value below 8.6 mm/mm2 to rule in DSP and an upper value of 15.3 mm/mm2 to rule out DSP were associated with 88% specificity and 88% sensitivity. Conclusions/interpretation: We established the diagnostic validity and common diagnostic thresholds for CNFL in type 1 and type 2 diabetes. Further research must determine to what extent CNFL can be deployed in clinical practice and in clinical trials assessing the efficacy of disease-modifying therapies for DSP.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalDiabetologia
DOIs
Publication statusAccepted/In press - 4 Jun 2018

Fingerprint

Diabetic Neuropathies
Nerve Fibers
Confocal Microscopy
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Area Under Curve
ROC Curve
Cohort Studies
Clinical Trials
Sensitivity and Specificity
Research

Keywords

  • Corneal confocal microscopy
  • Corneal nerves
  • Diabetic neuropathy
  • Diabetic sensorimotor polyneuropathy
  • Small nerve fibre morphology

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Corneal confocal microscopy for identification of diabetic sensorimotor polyneuropathy : a pooled multinational consortium study. / Perkins, Bruce A.; Lovblom, Leif E.; Bril, Vera; Scarr, Daniel; Ostrovski, Ilia; Orszag, Andrej; Edwards, Katie; Pritchard, Nicola; Russell, Anthony; Dehghani, Cirous; Pacaud, Danièle; Romanchuk, Kenneth; Mah, Jean K.; Jeziorska, Maria; Marshall, Andrew; Shtein, Roni M.; Pop-Busui, Rodica; Lentz, Stephen I.; Boulton, Andrew J.M.; Tavakoli, Mitra; Efron, Nathan; Malik, Rayaz.

In: Diabetologia, 04.06.2018, p. 1-6.

Research output: Contribution to journalArticle

Perkins, BA, Lovblom, LE, Bril, V, Scarr, D, Ostrovski, I, Orszag, A, Edwards, K, Pritchard, N, Russell, A, Dehghani, C, Pacaud, D, Romanchuk, K, Mah, JK, Jeziorska, M, Marshall, A, Shtein, RM, Pop-Busui, R, Lentz, SI, Boulton, AJM, Tavakoli, M, Efron, N & Malik, R 2018, 'Corneal confocal microscopy for identification of diabetic sensorimotor polyneuropathy: a pooled multinational consortium study', Diabetologia, pp. 1-6. https://doi.org/10.1007/s00125-018-4653-8
Perkins, Bruce A. ; Lovblom, Leif E. ; Bril, Vera ; Scarr, Daniel ; Ostrovski, Ilia ; Orszag, Andrej ; Edwards, Katie ; Pritchard, Nicola ; Russell, Anthony ; Dehghani, Cirous ; Pacaud, Danièle ; Romanchuk, Kenneth ; Mah, Jean K. ; Jeziorska, Maria ; Marshall, Andrew ; Shtein, Roni M. ; Pop-Busui, Rodica ; Lentz, Stephen I. ; Boulton, Andrew J.M. ; Tavakoli, Mitra ; Efron, Nathan ; Malik, Rayaz. / Corneal confocal microscopy for identification of diabetic sensorimotor polyneuropathy : a pooled multinational consortium study. In: Diabetologia. 2018 ; pp. 1-6.
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abstract = "Aims/hypothesis: Small cohort studies raise the hypothesis that corneal nerve abnormalities (including corneal nerve fibre length [CNFL]) are valid non-invasive imaging endpoints for diabetic sensorimotor polyneuropathy (DSP). We aimed to establish concurrent validity and diagnostic thresholds in a large cohort of participants with and without DSP. Methods: Nine hundred and ninety-eight participants from five centres (516 with type 1 diabetes and 482 with type 2 diabetes) underwent CNFL quantification and clinical and electrophysiological examination. AUC and diagnostic thresholds were derived and validated in randomly selected samples using receiver operating characteristic analysis. Sensitivity analyses included latent class models to address the issue of imperfect reference standard. Results: Type 1 and type 2 diabetes subcohorts had mean age of 42 ± 19 and 62 ± 10 years, diabetes duration 21 ± 15 and 12 ± 9 years and DSP prevalence of 31{\%} and 53{\%}, respectively. Derivation AUC for CNFL was 0.77 in type 1 diabetes (p < 0.001) and 0.68 in type 2 diabetes (p < 0.001) and was approximately reproduced in validation sets. The optimal threshold for automated CNFL was 12.5 mm/mm2 in type 1 diabetes and 12.3 mm/mm2 in type 2 diabetes. In the total cohort, a lower threshold value below 8.6 mm/mm2 to rule in DSP and an upper value of 15.3 mm/mm2 to rule out DSP were associated with 88{\%} specificity and 88{\%} sensitivity. Conclusions/interpretation: We established the diagnostic validity and common diagnostic thresholds for CNFL in type 1 and type 2 diabetes. Further research must determine to what extent CNFL can be deployed in clinical practice and in clinical trials assessing the efficacy of disease-modifying therapies for DSP.",
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AU - Perkins, Bruce A.

AU - Lovblom, Leif E.

AU - Bril, Vera

AU - Scarr, Daniel

AU - Ostrovski, Ilia

AU - Orszag, Andrej

AU - Edwards, Katie

AU - Pritchard, Nicola

AU - Russell, Anthony

AU - Dehghani, Cirous

AU - Pacaud, Danièle

AU - Romanchuk, Kenneth

AU - Mah, Jean K.

AU - Jeziorska, Maria

AU - Marshall, Andrew

AU - Shtein, Roni M.

AU - Pop-Busui, Rodica

AU - Lentz, Stephen I.

AU - Boulton, Andrew J.M.

AU - Tavakoli, Mitra

AU - Efron, Nathan

AU - Malik, Rayaz

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N2 - Aims/hypothesis: Small cohort studies raise the hypothesis that corneal nerve abnormalities (including corneal nerve fibre length [CNFL]) are valid non-invasive imaging endpoints for diabetic sensorimotor polyneuropathy (DSP). We aimed to establish concurrent validity and diagnostic thresholds in a large cohort of participants with and without DSP. Methods: Nine hundred and ninety-eight participants from five centres (516 with type 1 diabetes and 482 with type 2 diabetes) underwent CNFL quantification and clinical and electrophysiological examination. AUC and diagnostic thresholds were derived and validated in randomly selected samples using receiver operating characteristic analysis. Sensitivity analyses included latent class models to address the issue of imperfect reference standard. Results: Type 1 and type 2 diabetes subcohorts had mean age of 42 ± 19 and 62 ± 10 years, diabetes duration 21 ± 15 and 12 ± 9 years and DSP prevalence of 31% and 53%, respectively. Derivation AUC for CNFL was 0.77 in type 1 diabetes (p < 0.001) and 0.68 in type 2 diabetes (p < 0.001) and was approximately reproduced in validation sets. The optimal threshold for automated CNFL was 12.5 mm/mm2 in type 1 diabetes and 12.3 mm/mm2 in type 2 diabetes. In the total cohort, a lower threshold value below 8.6 mm/mm2 to rule in DSP and an upper value of 15.3 mm/mm2 to rule out DSP were associated with 88% specificity and 88% sensitivity. Conclusions/interpretation: We established the diagnostic validity and common diagnostic thresholds for CNFL in type 1 and type 2 diabetes. Further research must determine to what extent CNFL can be deployed in clinical practice and in clinical trials assessing the efficacy of disease-modifying therapies for DSP.

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KW - Corneal confocal microscopy

KW - Corneal nerves

KW - Diabetic neuropathy

KW - Diabetic sensorimotor polyneuropathy

KW - Small nerve fibre morphology

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