C-Fiber Assays in the Cornea vs. Skin

Moulton, Eric A.; Borsook, David

doi:10.3390/brainsci9110320

Cited by 15 publications

(12 citation statements)

References 131 publications

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“…The greater corneal nerve loss in patients with DPN compared with those without DPN is consistent with studies showing that corneal nerve loss is associated with the severity of DPN 4,24,51,57,58 and has good sensitivity and specificity for diagnosing DPN [5][6][7] . Both CNFD and IENFD have a comparable diagnostic performance for DPN 8,9,59 , although in a study of patients with recently diagnosed type 2 diabetes there were differences in the extent of small nerve fiber damage between CCM and skin biopsy 57 . Additionally, a reduction in corneal nerve parameters is associated with incident DPN 10,53,60 and greater corneal nerve loss 41 , and augmented nerve branching 27 occurs in patients with painful diabetic neuropathy.…”

Section: Discussionmentioning

confidence: 96%

Corneal confocal microscopy for the diagnosis of diabetic peripheral neuropathy: A systematic review and meta‐analysis

Gad

Petropoulos

Khan

et al. 2021

J of Diabetes Invest

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Introduction: Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that identifies corneal nerve fiber damage. Small studies suggest that CCM could be used to assess patients with diabetic peripheral neuropathy (DPN). Aim: To undertake a systematic review and meta-analysis assessing the diagnostic utility of CCM for sub-clinical DPN (DPN -) and established DPN (DPN + ). Data sources: Databases (PubMed, Embase, Central, ProQuest) were searched for studies using CCM in patients with diabetes up to April 2020. Study selection: Studies were included if they reported on at least one CCM parameter in patients with diabetes. Data extraction: Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and inferior whorl length (IWL) were compared between patients with diabetes with and without DPN and controls. Meta-analysis was undertaken using RevMan V.5.3. Data synthesis: Thirty-eight studies including ~4,000 participants were included in this meta-analysis. There were significant reductions in CNFD, CNBD, CNFL, and IWL in DPNvs controls (P < 0.00001), DPN + vs controls (P < 0.00001), and DPN + vs DPN -(P < 0.00001). Conclusion: This systematic review and meta-analysis shows that CCM detects small nerve fiber loss in subclinical and clinical DPN and concludes that CCM has good diagnostic utility in DPN.

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Section: Discussionmentioning

confidence: 96%

Corneal confocal microscopy for the diagnosis of diabetic peripheral neuropathy: A systematic review and meta‐analysis

Gad

Petropoulos

Khan

et al. 2021

J of Diabetes Invest

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“…Five main etiological processes underlie SFN ( Table 1 ) [ 15 , 16 ], although approximately 40% of cases remain idiopathic [ 15 , 16 , 17 ]. Previously, it was considered that most cases of SFN were associated with diabetes mellitus type 1 and 2.…”

Section: Etiology and Manifestations Of Small Fiber Neuropathymentioning

confidence: 99%

“…CCM is gaining acceptance in the diagnosis of small fiber neuropathy ( Figure 2 ) [ 36 ]. Earlier studies of patients with idiopathic SFN demonstrated decreased corneal nerve fiber density and increased tortuosity [ 29 , 36 ] with increased dendritic cells, indicating systemic inflammation [ 15 ]. In a recent deep phenotyping study of patients with idiopathic SFN, whilst abnormalities occurred in the distal intraepidermal nerve fiber density (IENFD) (60/86, 70%) and neurological examination (53/86, 62%) most frequently reflected small fiber disease, adding CCM and/or pain-related evoked potentials (PREP) further increased the identification of patients with small fiber impairment to 47/55 (85%), whilst quantitative sensory testing (QST), quantitative sudomotor reflex testing (QSART), and proximal IENFD were of lower impact [ 15 , 37 ].…”

Section: Corneal Confocal Microscopy In Small Fiber Neuropathymentioning

confidence: 99%

Corneal Confocal Microscopy in the Diagnosis of Small Fiber Neuropathy: Faster, Easier, and More Efficient Than Skin Biopsy?

et al. 2021

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Chronic pain may affect 30–50% of the world’s population and an important cause is small fiber neuropathy (SFN). Recent research suggests that autoimmune diseases may be one of the most common causes of small nerve fiber damage. There is low awareness of SFN among patients and clinicians and it is difficult to diagnose as routine electrophysiological methods only detect large fiber abnormalities, and specialized small fiber tests, like skin biopsy and quantitative sensory testing, are not routinely available. Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible method for quantifying small nerve fiber degeneration and regeneration, and could be an important tool for diagnosing SFN. This review considers the advantages and disadvantages of CCM and highlights the evolution of this technique from a research tool to a diagnostic test for small fiber damage, which can be a valuable contribution to the study and management of autoimmune disease.

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“…It provides various morphometric parameters to quantify corneal nociceptors and their changes over time. Use of this tool is limited in that it requires specific equipment and a trained technician that are often unavailable, thus it is primarily used in research at this time [ 6 , 26 , 27 , 28 ].…”

Section: Evaluation Of Sfnmentioning

confidence: 99%

Intraepidermal Nerve Fiber Density as Measured by Skin Punch Biopsy as a Marker for Small Fiber Neuropathy: Application in Patients with Fibromyalgia

Kelley

Hackshaw

2021

Diagnostics

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Small fiber neuropathy (SFN) is a type of peripheral neuropathy that occurs from damage to the small A-delta and C nerve fibers that results in the clinical condition known as SFN. This pathology may be the result of metabolic, toxic, immune-mediated, and/or genetic factors. Small fiber symptoms can be variable and inconsistent and therefore require an objective biomarker confirmation. Small fiber dysfunction is not typically captured by diagnostic tests for large-fiber neuropathy (nerve conduction and electromyographic study). Therefore, skin biopsies stained with PGP 9.5 are the universally recommended objective test for SFN, with quantitative sensory tests, autonomic function testing, and corneal confocal imaging as secondary or adjunctive choices. Fibromyalgia (FM) is a heterogenous syndrome that has many symptoms that overlap with those found in SFN. A growing body of research has shown approximately 40–60% of patients carrying a diagnosis of FM have evidence of SFN on skin punch biopsy. There is currently no clearly defined phenotype in FM at this time to suggest whom may or may not have SFN, though research suggests it may correlate with severe cases. The skin punch biopsy provides an objective tool for use in quantifying small fiber pathology in FM. Skin punch biopsy may also be repeated for surveillance of the disease as well as measuring response to treatments. Evaluation of SFN in FM allows for better classification of FM and guidance for patient care as well as validation for their symptoms, leading to better use of resources and outcomes.

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C-Fiber Assays in the Cornea vs. Skin

Cited by 15 publications

References 131 publications

Corneal confocal microscopy for the diagnosis of diabetic peripheral neuropathy: A systematic review and meta‐analysis

Corneal confocal microscopy for the diagnosis of diabetic peripheral neuropathy: A systematic review and meta‐analysis

Corneal Confocal Microscopy in the Diagnosis of Small Fiber Neuropathy: Faster, Easier, and More Efficient Than Skin Biopsy?

Intraepidermal Nerve Fiber Density as Measured by Skin Punch Biopsy as a Marker for Small Fiber Neuropathy: Application in Patients with Fibromyalgia

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