Corneal confocal microscopy detects small nerve fibre damage in patients with painful diabetic neuropathy

Alise Kalteniece,Maryam Ferdousi,Rayaz A Malik,Catharina G Faber,Womba M Mubita,Handrean Soran,Giuseppe Lauria,Shazli Azmi,Andrew Marshall

doi:10.1038/s41598-020-60422-7

Abstract

Neuropathic pain is believed to arise from damage to nociceptive C fibres in diabetic neuropathy (DN). We have utilised corneal confocal microscopy (CCM) to quantify the severity of small nerve fibre damage in relation to the severity of neuropathic pain and quality of life (QoL) in patients with and without painful DN. 30 controls and patients with painful (n = 78) and painless (n = 62) DN underwent assessment of large and small nerve fibre function, CCM, neuropathic symptoms (small fibre neuropathy symptom inventory questionnaire, neuropathic pain scale) and QoL (SF-36, pre-R-ODS and hospital anxiety and depression scale). Patients with painful compared to painless DN, had comparable neurophysiology and vibration perception, but lower corneal nerve fibre density (20.1 ± 0.87 vs. 24.13 ± 0.91, P = 0.005), branch density (44.4 ± 3.31 vs. 57.74 ± 3.98, P = 0.03), length (19.61 ± 0.81 vs. 22.77 ± 0.83, P = 0.01), inferior whorl length (18.03 ± 1.46 vs. 25.1 ± 1.95, P = 0.005) and cold sensation threshold (21.35 ± 0.99 vs. 26.08 ± 0.5, P < 0.0001) and higher warm sensation threshold (43.7 ± 0.49 vs. 41.37 ± 0.51, P = 0.004) indicative of small fibre damage. There was a significant association between all CCM parameters and the severity of painful neuropathic symptoms, depression score and QoL. CCM identifies small nerve fibre loss, which correlates with the severity of neuropathic symptoms and reduced QoL in patients with painful diabetic neuropathy.

Highlights

Neuropathic pain is believed to arise from damage to nociceptive C fibres in diabetic neuropathy (DN)
The duration of diabetes was comparable between patients with painless and painful DN. 58% of patients with PDN were on pain medications
Previous studies have reported that damage to Aδ and C fibres is associated with neuropathic pain[30,31]

Summary

Introduction

Neuropathic pain is believed to arise from damage to nociceptive C fibres in diabetic neuropathy (DN). CCM identifies small nerve fibre loss, which correlates with the severity of neuropathic symptoms and reduced QoL in patients with painful diabetic neuropathy. The diagnosis of painful DN is challenging and subjective, based on establishing neurologic deficits and identifying the type and severity of pain through validated questionnaires[14] including neuropathic pain scale (NPS)[15], small fibre neuropathy symptom inventory questionnaire (SFN-SIQ)[16] and quality of life (QoL) through the hospital anxiety and depression scale (HADS)[17] and the 36-item short form health survey (SF-36)[18]. LDL – low-density lipoprotein cholesterol, VPT – vibration perception threshold, NDS – neuropathy disability score, CNFD – corneal nerve fibre density, CNBD – corneal nerve fibre branch density, CNFL – corneal nerve fibre length, IWL – inferior whorl length. ^P < 0.05 compared to controls, *P < 0.05 compared to painless

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