Determining the accuracy of changes in the nerves in the cornea using a method called corneal confocal microscopy to identify small nerve fibre damage in patients with fibromyalgia

Diabetic peripheral neuropathy (DPN) is the most common complication of both type 1 and 2 diabetes. As a result, neuropathic pain, diabetic foot ulcers and lower-limb amputations impact drastically on quality of life, contributing to the individual, societal, financial and healthcare burden of diabetes. DPN is diagnosed at a late, often pre-ulcerative stage due to a lack of early systematic screening and the endorsement of monofilament testing which identifies advanced neuropathy only. Compared to the success of the diabetic eye and kidney screening programmes there is clearly an unmet need for an objective reliable biomarker for the detection of early DPN. This article critically appraises research and clinical methods for the diagnosis or screening of early DPN. In brief, functional measures are subjective and are difficult to implement due to technical complexity. Moreover, skin biopsy is invasive, expensive and lacks diagnostic laboratory capacity. Indeed, point-of-care nerve conduction tests are convenient and easy to implement however questions are raised regarding their suitability for use in screening due to the lack of small nerve fibre evaluation. Corneal confocal microscopy (CCM) is a rapid, non-invasive, and reproducible technique to quantify small nerve fibre damage and repair which can be conducted alongside retinopathy screening. CCM identifies early sub-clinical DPN, predicts the development and allows staging of DPN severity. Automated quantification of CCM with AI has enabled enhanced unbiased quantification of small nerve fibres and potentially early diagnosis of DPN. Improved screening tools will prevent and reduce the burden of foot ulceration and amputations with the primary aim of reducing the prevalence of this common microvascular complication.

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Using corneal confocal microscopy to compare Mecobalamin intramuscular injections vs oral tablets in treating diabetic peripheral neuropathy: a RCT

Scientific Reports ◽

10.1038/s41598-021-94284-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuanjin Zhang ◽

Dongsheng Fan ◽

Yixuan Zhang ◽

Shuo Zhang ◽

Haikun Wang ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Confocal Microscopy ◽

Nerve Fibre ◽

Diabetic Peripheral Neuropathy ◽

Controlled Study ◽

Oral Tablet ◽

Injection Treatment ◽

Intramuscular Injections ◽

Corneal Confocal Microscopy ◽

Corneal Nerve

AbstractThis randomized controlled study used corneal confocal microscopy (CCM) to compare the efficacy of Mecobalamin intramuscular injections vs oral tablets in treating mild to moderate diabetic peripheral neuropathy (DPN) by detecting early nerve fiber repair. Enrolled patients were randomized approximately 1:1 to receive Mecobalamin intramuscular injections (0.5 mg/day, 3 times/week) or Mecobalamin oral tablets (1.5 mg/day) for 8 weeks. Primary outcome was change of inferior whorl length (IWL) from baseline. Secondary outcomes included changes of corneal nerve fibre length (CNFL), corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and the Survey of Autonomic Symptoms (SAS). 15 (93.75%) patients in the injection group and 17 (89.47%) patients in the tablet group completed the study. The injection treatment significantly improved patients’ IWL from baseline (21.64 ± 3.00 mm/mm2 vs 17.64 ± 4.83 mm/mm2, P < 0.01) while the tablet treatment didn’t. Additionally, the injection treatment led to significantly improved CNFL, CNBD and SAS from baseline (all P < 0.05) while the tablet treatment did not. No patient experienced any adverse events. In conclusion, CCM is sensitive enough to detect the superior efficacy of 8-week Mecobalamin intramuscular injection treatment for DPN compared to the oral tablet treatment.ClinicalTrials.gov registration number: NCT04372316 (30/04/2020).

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A novel investigation method for axonal damage in neuromyelitis optica spectrum disorder: In vivo corneal confocal microscopy

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217321998060 ◽

2021 ◽

Vol 7 (1) ◽

pp. 205521732199806

Author(s):

Ayşe Altıntaş ◽

Ayse Yildiz-Tas ◽

Sezen Yilmaz ◽

Betul N Bayraktutar ◽

Melis Cansu Comert ◽

...

Keyword(s):

Confocal Microscopy ◽

Nerve Fibre ◽

Disease Severity ◽

Neuromyelitis Optica ◽

Spectrum Disorder ◽

Neuromyelitis Optica Spectrum Disorder ◽

Rnfl Thickness ◽

Corneal Confocal Microscopy ◽

Corneal Nerve

Background Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disorder that damages optic nerves, brainstem, and spinal cord. In vivo corneal confocal microscopy (IVCM) is a noninvasive technique that provides corneal images with dendritic cells (DCs) and corneal subbasal nerve plexus (SBP), which arises from the trigeminal nerve. Objective We investigated corneal SBP changes in NMOSD and proposed IVCM as a potential new disease severity biomarker for NMOSD. Methods Seventeen age-sex matched NMOSD patients and 19 healthy participants underwent complete neurologic and ophthalmologic examinations. The duration of disease, first symptom, presence of optic neuritis attack, antibody status, Expanded Disability Status Scale(EDSS) score and disease severity score(DSS) were recorded. Retinal nerve fibre layer (RNFL) thickness was measured with optical coherence tomography, and corneal SBP images were taken with IVCM. Results NMOSD patients had significantly reduced corneal nerve fibre lenght-density and corneal nerve branch lenght-density compared with controls, while DC density was increased. NMOSD patients also showed significantly reduced RNFL thickness compared with controls. EDSS,DSS levels were inversely correlated with IVCM parameters. Conclusion We observed significant corneal nerve fibre loss in NMOSD patients in relation to disease severity. IVCM can be a candidate noninvasive imaging method for axonal damage assessment in NMOSD that warrants further investigation.

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Small Nerve Fiber Quantification in the Diagnosis of Diabetic Sensorimotor Polyneuropathy: Comparing Corneal Confocal Microscopy With Intraepidermal Nerve Fiber Density

Diabetes Care ◽

10.2337/dc14-2422 ◽

2015 ◽

Vol 38 (6) ◽

pp. 1138-1144 ◽

Cited By ~ 96

Author(s):

Xin Chen ◽

Jim Graham ◽

Mohammad A. Dabbah ◽

Ioannis N. Petropoulos ◽

Georgios Ponirakis ◽

...

Keyword(s):

Confocal Microscopy ◽

Nerve Fiber ◽

Fiber Density ◽

Sensorimotor Polyneuropathy ◽

Corneal Confocal Microscopy ◽

Intraepidermal Nerve Fiber Density ◽

Nerve Fiber Density ◽

Intraepidermal Nerve Fiber ◽

Small Nerve

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Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-319450 ◽

2021 ◽

pp. bjophthalmol-2021-319450

Author(s):

Gulfidan Bitirgen ◽

Celalettin Korkmaz ◽

Adil Zamani ◽

Ahmet Ozkagnici ◽

Nazmi Zengin ◽

...

Keyword(s):

Confocal Microscopy ◽

Nerve Fibre ◽

Fibre Length ◽

Neurological Symptoms ◽

University Hospital ◽

Nerve Branch ◽

Cross Sectional ◽

Corneal Confocal Microscopy ◽

Corneal Nerve ◽

Fibre Loss

Background/AimsLong COVID is characterised by a range of potentially debilitating symptoms which develop in at least 10% of people who have recovered from acute SARS-CoV-2 infection. This study has quantified corneal sub-basal nerve plexus morphology and dendritic cell (DC) density in patients with and without long COVID.MethodsForty subjects who had recovered from COVID-19 and 30 control participants were included in this cross-sectional comparative study undertaken at a university hospital. All patients underwent assessment with the National Institute for Health and Care Excellence (NICE) long COVID, Douleur Neuropathique 4 (DN4) and Fibromyalgia questionnaires, and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), and total, mature and immature DC density.ResultsThe mean time after the diagnosis of COVID-19 was 3.7±1.5 months. Patients with neurological symptoms 4 weeks after acute COVID-19 had a lower CNFD (p=0.032), CNBD (p=0.020), and CNFL (p=0.012), and increased DC density (p=0.046) compared with controls, while patients without neurological symptoms had comparable corneal nerve parameters, but increased DC density (p=0.003). There were significant correlations between the total score on the NICE long COVID questionnaire at 4 and 12 weeks with CNFD (ρ=−0.436; p=0.005, ρ=−0.387; p=0.038, respectively) and CNFL (ρ=−0.404; p=0.010, ρ=−0.412; p=0.026, respectively).ConclusionCorneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID, especially those with neurological symptoms. CCM could be used to objectively identify patients with long COVID.

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

Pathophysiology ◽

10.3390/pathophysiology29010001 ◽

2021 ◽

Vol 29 (1) ◽

pp. 1-8

Author(s):

Mariia V. Lukashenko ◽

Natalia Y. Gavrilova ◽

Anna V. Bregovskaya ◽

Lidiia A. Soprun ◽

Leonid P. Churilov ◽

...

Keyword(s):

Confocal Microscopy ◽

Skin Biopsy ◽

Nerve Fiber ◽

Small Fiber Neuropathy ◽

Fiber Damage ◽

Advantages And Disadvantages ◽

Small Fiber ◽

Corneal Confocal Microscopy ◽

Common Causes ◽

Small Nerve

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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