Early detection of diabetic peripheral neuropathy with corneal confocal microscopy

Hossain, Parwez; Sachdev, Arun; Malik, Rayaz A.

doi:10.1016/s0140-6736(05)67546-0

Cited by 145 publications

(117 citation statements)

References 15 publications

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“…Unmyelinated nerve fibers can now be examined at approximately original magnification 3500 using a laser scanning corneal confocal microscope (CCM) to image the subbasal nerve plexus of the human cornea in vivo (2). This approach has been validated as a viable alternative for assessing DPN (3)(4)(5). Increased severity of DPN is associated with reduced corneal nerve fiber length (CNFL) (4,5) and corneal sensitivity (6,7), assessed using CCM and noncontact corneal esthesiometry (NCCE), respectively.…”

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confidence: 99%

Corneal Confocal Microscopy Predicts 4-Year Incident Peripheral Neuropathy in Type 1 Diabetes

et al. 2015

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OBJECTIVEThis study determined if deficits in corneal nerve fiber length (CNFL) assessed using corneal confocal microscopy (CCM) can predict future onset of diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODSCNFL and a range of other baseline measures were compared between 90 nonneuropathic patients with type 1 diabetes who did or did not develop DPN after 4 years. The receiver operator characteristic (ROC) curve was used to determine the capability of single and combined measures of neuropathy to predict DPN. RESULTSDPN developed in 16 participants (18%) after 4 years. Factors predictive of 4-year incident DPN were lower CNFL (P = 0.041); longer duration of diabetes (P = 0.002); higher triglycerides (P = 0.023); retinopathy (higher on the Early Treatment of Diabetic Retinopathy Study scale) (P = 0.008); nephropathy (higher albumin-tocreatinine ratio) (P = 0.001); higher neuropathy disability score (P = 0.037); lower cold sensation (P = 0.001) and cold pain (P = 0.027) thresholds; higher warm sensation (P = 0.008), warm pain (P = 0.024), and vibration (P = 0.003) thresholds; impaired monofilament response (P = 0.003); and slower peroneal (P = 0.013) and sural (P = 0.002) nerve conduction velocity. CCM could predict the 4-year incident DPN with 63% sensitivity and 74% specificity for a CNFL threshold cutoff of 14.1 mm/mm 2 (area under ROC curve = 0.66, P = 0.041). Combining neuropathy measures did not improve predictive capability. CONCLUSIONS DPN can be predicted by various demographic, metabolic, and conventional neuropathy measures. The ability of CCM to predict DPN broadens the already impressive diagnostic capabilities of this novel ophthalmic marker.Diabetic peripheral neuropathy (DPN) can result in pain, foot ulceration, and lower extremity amputation (1). Unmyelinated nerve fibers can now be examined at approximately original magnification 3500 using a laser scanning corneal confocal microscope (CCM) to image the subbasal nerve plexus of the human cornea in vivo (2). This approach has been validated as a viable alternative for assessing DPN (3-5). Increased severity of DPN is associated with reduced corneal nerve fiber length (CNFL) (4,5) and corneal sensitivity (6,7), assessed using CCM and noncontact corneal esthesiometry (NCCE), respectively.

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confidence: 99%

Corneal Confocal Microscopy Predicts 4-Year Incident Peripheral Neuropathy in Type 1 Diabetes

et al. 2015

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“…Corneal nerve fibers exert important trophic influences and contribute to the maintenance of corneal epithelium homeostasis, whereas the dysfunction of corneal innervation produces an impairment of corneal epithelial wound healing, known as neurotrophic keratitis, as caused by for instance herpetic viral infections, trigeminal nerve damage, or diabetes (27)(28)(29). Although tear fluid impairment is also involved (30), the neurotrophic deficits may play a major role in the pathogenesis of diabetic keratopathy, as the density of corneal nerve fibers and corneal sensation decreased in diabetic patients (31)(32)(33). However, although being the major sensory neurotransmitter and neuropeptide released from corneal nerve fibers, SP was shown not to be significantly decreased in diabetic cornea (34).…”

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Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor

et al. 2014

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Substance P (SP) is a neuropeptide, predominantly released from sensory nerve fibers, with a potentially protective role in diabetic corneal epithelial wound healing. However, the molecular mechanism remains unclear. We investigated the protective mechanism of SP against hyperglycemia-induced corneal epithelial wound healing defects, using type 1 diabetic mice and high glucose–treated corneal epithelial cells. Hyperglycemia induced delayed corneal epithelial wound healing, accompanied by attenuated corneal sensation, mitochondrial dysfunction, and impairments of Akt, epidermal growth factor receptor (EGFR), and Sirt1 activation, as well as decreased reactive oxygen species (ROS) scavenging capacity. However, SP application promoted epithelial wound healing, recovery of corneal sensation, improvement of mitochondrial function, and reactivation of Akt, EGFR, and Sirt1, as well as increased ROS scavenging capacity, in both diabetic mouse corneal epithelium and high glucose–treated corneal epithelial cells. The promotion of SP on diabetic corneal epithelial healing was completely abolished by a neurokinin-1 (NK-1) receptor antagonist. Moreover, the subconjunctival injection of NK-1 receptor antagonist also caused diabetic corneal pathological changes in normal mice. In conclusion, the results suggest that SP-NK-1 receptor signaling plays a critical role in the maintenance of corneal epithelium homeostasis, and that SP signaling through the NK-1 receptor contributes to the promotion of diabetic corneal epithelial wound healing by rescued activation of Akt, EGFR, and Sirt1, improvement of mitochondrial function, and increased ROS scavenging capacity.

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“…We have assessed corneal sensitivity in a large group of diabetic patients using both C-BA and NCCA to assess concordance between the two methods and also to define whether C-nerve fibers are the earliest to undergo damage (15). Using corneal confocal microscopy, we have previously shown that corneal nerve fiber damage is directly related to the severity of somatic neuropathy (16,17).…”

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Corneal Sensitivity Is Reduced and Relates to the Severity of Neuropathy in Patients With Diabetes

et al. 2007

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Early detection of diabetic peripheral neuropathy with corneal confocal microscopy

Cited by 145 publications

References 15 publications

Corneal Confocal Microscopy Predicts 4-Year Incident Peripheral Neuropathy in Type 1 Diabetes

Corneal Confocal Microscopy Predicts 4-Year Incident Peripheral Neuropathy in Type 1 Diabetes

Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor

Corneal Sensitivity Is Reduced and Relates to the Severity of Neuropathy in Patients With Diabetes

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