The inferior whorl for detecting diabetic peripheral neuropathy using corneal confocal microscopy

Ioannis N. Petropoulos, Maryam Ferdousi, Andrew Marshall, Uazman Alam, Georgios Ponirakis, Shazli Azmi, Hassan Fadavi, Nathan Efron, Mitra Tavakoli, Rayaz Malik

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

PURPOSE. In vivo corneal confocal microscopy (CCM) is increasingly used as a surrogate endpoint in studies of diabetic polyneuropathy (DPN). However, it is not clear whether imaging the central cornea provides optimal diagnostic utility for DPN. Therefore, we compared nerve morphology in the central cornea and the inferior whorl, a more distal and densely innervated area located inferior and nasal to the central cornea. METHODS. A total of 53 subjects with type 1/type 2 diabetes and 15 age-matched control subjects underwent detailed assessment of neuropathic symptoms (NPS), deficits (neuropathy disability score [NDS]), quantitative sensory testing (vibration perception threshold [VPT], cold and warm threshold [CT/WT], and cold-and heat-induced pain [CIP/HIP]), and electrophysiology (sural and peroneal nerve conduction velocity [SSNCV/PMNCV], and sural and peroneal nerve amplitude [SSNA/PMNA]) to diagnose patients with (DPN+) and without (DPN-) neuropathy. Corneal nerve fiber density (CNFD) and length (CNFL) in the central cornea, and inferior whorl length (IWL) were quantified. RESULTS. Comparing control subjects to DPN- and DPN+' patients, there was a significant increase in NDS (0 vs. 2.6 ± 2.3 vs. 3.3±2.7, P < 0.01), VPT (V; 5.4±3.0 vs. 10.6±10.3 vs. 17.7±11.8, P < 0.01), WT (°C; 37.7±3.5 vs. 39.1±5.1 vs. 41.7±4.7, P < 0.05), and a significant decrease in SSNCV (m/s; 50.2±5.4 vs. 48.4±5.0 vs. 39.5±10.6, P < 0.05), CNFD (fibers/mm2; 37.8±4.9 vs. 29.7±7.7 vs. 27.1±9.9, P < 0.01), CNFL (mm/mm2; 27.5±3.6 vs. 24.4±7.8 vs. 20.7±7.1, P < 0.01), and IWL (mm/mm2; 35.1±6.5 vs. 26.2±10.5 vs. 23.6±11.4, P < 0.05). For the diagnosis of DPN, CNFD, CNFL, and IWL achieved an area under the curve (AUC) of 0.75, 0.74, and 0.70, respectively, and a combination of IWL- CNFD achieved an AUC of 0.76. CONCLUSIONS. The parameters of CNFD, CNFL, and IWL have a comparable ability to diagnose patients with DPN. However, IWL detects an abnormality even in patients without DPN. Combining IWL with CNFD may improve the diagnostic performance of CCM.

Original languageEnglish
Pages (from-to)2498-2504
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number4
DOIs
Publication statusPublished - 2015

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Diabetic Neuropathies
Peripheral Nervous System Diseases
Confocal Microscopy
Nerve Fibers
Cornea
Sural Nerve
Peroneal Nerve
Vibration
Area Under Curve
Aptitude
Symptom Assessment
Electrophysiology
Neural Conduction
Type 1 Diabetes Mellitus
Nose
Type 2 Diabetes Mellitus
Hot Temperature
Biomarkers
Pain

Keywords

  • Corneal confocal microscopy
  • Diabetic neuropathy
  • Image analysis

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

The inferior whorl for detecting diabetic peripheral neuropathy using corneal confocal microscopy. / Petropoulos, Ioannis N.; Ferdousi, Maryam; Marshall, Andrew; Alam, Uazman; Ponirakis, Georgios; Azmi, Shazli; Fadavi, Hassan; Efron, Nathan; Tavakoli, Mitra; Malik, Rayaz.

In: Investigative Ophthalmology and Visual Science, Vol. 56, No. 4, 2015, p. 2498-2504.

Research output: Contribution to journalArticle

Petropoulos, IN, Ferdousi, M, Marshall, A, Alam, U, Ponirakis, G, Azmi, S, Fadavi, H, Efron, N, Tavakoli, M & Malik, R 2015, 'The inferior whorl for detecting diabetic peripheral neuropathy using corneal confocal microscopy', Investigative Ophthalmology and Visual Science, vol. 56, no. 4, pp. 2498-2504. https://doi.org/10.1167/iovs.14-15919
Petropoulos, Ioannis N. ; Ferdousi, Maryam ; Marshall, Andrew ; Alam, Uazman ; Ponirakis, Georgios ; Azmi, Shazli ; Fadavi, Hassan ; Efron, Nathan ; Tavakoli, Mitra ; Malik, Rayaz. / The inferior whorl for detecting diabetic peripheral neuropathy using corneal confocal microscopy. In: Investigative Ophthalmology and Visual Science. 2015 ; Vol. 56, No. 4. pp. 2498-2504.
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TY - JOUR

T1 - The inferior whorl for detecting diabetic peripheral neuropathy using corneal confocal microscopy

AU - Petropoulos, Ioannis N.

AU - Ferdousi, Maryam

AU - Marshall, Andrew

AU - Alam, Uazman

AU - Ponirakis, Georgios

AU - Azmi, Shazli

AU - Fadavi, Hassan

AU - Efron, Nathan

AU - Tavakoli, Mitra

AU - Malik, Rayaz

PY - 2015

Y1 - 2015

N2 - PURPOSE. In vivo corneal confocal microscopy (CCM) is increasingly used as a surrogate endpoint in studies of diabetic polyneuropathy (DPN). However, it is not clear whether imaging the central cornea provides optimal diagnostic utility for DPN. Therefore, we compared nerve morphology in the central cornea and the inferior whorl, a more distal and densely innervated area located inferior and nasal to the central cornea. METHODS. A total of 53 subjects with type 1/type 2 diabetes and 15 age-matched control subjects underwent detailed assessment of neuropathic symptoms (NPS), deficits (neuropathy disability score [NDS]), quantitative sensory testing (vibration perception threshold [VPT], cold and warm threshold [CT/WT], and cold-and heat-induced pain [CIP/HIP]), and electrophysiology (sural and peroneal nerve conduction velocity [SSNCV/PMNCV], and sural and peroneal nerve amplitude [SSNA/PMNA]) to diagnose patients with (DPN+) and without (DPN-) neuropathy. Corneal nerve fiber density (CNFD) and length (CNFL) in the central cornea, and inferior whorl length (IWL) were quantified. RESULTS. Comparing control subjects to DPN- and DPN+' patients, there was a significant increase in NDS (0 vs. 2.6 ± 2.3 vs. 3.3±2.7, P < 0.01), VPT (V; 5.4±3.0 vs. 10.6±10.3 vs. 17.7±11.8, P < 0.01), WT (°C; 37.7±3.5 vs. 39.1±5.1 vs. 41.7±4.7, P < 0.05), and a significant decrease in SSNCV (m/s; 50.2±5.4 vs. 48.4±5.0 vs. 39.5±10.6, P < 0.05), CNFD (fibers/mm2; 37.8±4.9 vs. 29.7±7.7 vs. 27.1±9.9, P < 0.01), CNFL (mm/mm2; 27.5±3.6 vs. 24.4±7.8 vs. 20.7±7.1, P < 0.01), and IWL (mm/mm2; 35.1±6.5 vs. 26.2±10.5 vs. 23.6±11.4, P < 0.05). For the diagnosis of DPN, CNFD, CNFL, and IWL achieved an area under the curve (AUC) of 0.75, 0.74, and 0.70, respectively, and a combination of IWL- CNFD achieved an AUC of 0.76. CONCLUSIONS. The parameters of CNFD, CNFL, and IWL have a comparable ability to diagnose patients with DPN. However, IWL detects an abnormality even in patients without DPN. Combining IWL with CNFD may improve the diagnostic performance of CCM.

AB - PURPOSE. In vivo corneal confocal microscopy (CCM) is increasingly used as a surrogate endpoint in studies of diabetic polyneuropathy (DPN). However, it is not clear whether imaging the central cornea provides optimal diagnostic utility for DPN. Therefore, we compared nerve morphology in the central cornea and the inferior whorl, a more distal and densely innervated area located inferior and nasal to the central cornea. METHODS. A total of 53 subjects with type 1/type 2 diabetes and 15 age-matched control subjects underwent detailed assessment of neuropathic symptoms (NPS), deficits (neuropathy disability score [NDS]), quantitative sensory testing (vibration perception threshold [VPT], cold and warm threshold [CT/WT], and cold-and heat-induced pain [CIP/HIP]), and electrophysiology (sural and peroneal nerve conduction velocity [SSNCV/PMNCV], and sural and peroneal nerve amplitude [SSNA/PMNA]) to diagnose patients with (DPN+) and without (DPN-) neuropathy. Corneal nerve fiber density (CNFD) and length (CNFL) in the central cornea, and inferior whorl length (IWL) were quantified. RESULTS. Comparing control subjects to DPN- and DPN+' patients, there was a significant increase in NDS (0 vs. 2.6 ± 2.3 vs. 3.3±2.7, P < 0.01), VPT (V; 5.4±3.0 vs. 10.6±10.3 vs. 17.7±11.8, P < 0.01), WT (°C; 37.7±3.5 vs. 39.1±5.1 vs. 41.7±4.7, P < 0.05), and a significant decrease in SSNCV (m/s; 50.2±5.4 vs. 48.4±5.0 vs. 39.5±10.6, P < 0.05), CNFD (fibers/mm2; 37.8±4.9 vs. 29.7±7.7 vs. 27.1±9.9, P < 0.01), CNFL (mm/mm2; 27.5±3.6 vs. 24.4±7.8 vs. 20.7±7.1, P < 0.01), and IWL (mm/mm2; 35.1±6.5 vs. 26.2±10.5 vs. 23.6±11.4, P < 0.05). For the diagnosis of DPN, CNFD, CNFL, and IWL achieved an area under the curve (AUC) of 0.75, 0.74, and 0.70, respectively, and a combination of IWL- CNFD achieved an AUC of 0.76. CONCLUSIONS. The parameters of CNFD, CNFL, and IWL have a comparable ability to diagnose patients with DPN. However, IWL detects an abnormality even in patients without DPN. Combining IWL with CNFD may improve the diagnostic performance of CCM.

KW - Corneal confocal microscopy

KW - Diabetic neuropathy

KW - Image analysis

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