Corneal confocal microscopy for identification of diabetic sensorimotor polyneuropathy: a pooled multinational consortium study

Perkins, Bruce A.; Lovblom, Leif E.; Bril, Vera; Scarr, Daniel; Ostrovski, Ilia; Orszag, Andrej; Edwards, Katie; Pritchard, Nicola; Russell, Anthony; Dehghani, Cirous; Pacaud, Danièle; Romanchuk, Kenneth; Mah, Jean K.; Jeziorska, Maria; Marshall, Andrew; Shtein, Roni M.; Pop‐Busui, Rodica; Lentz, Stephen I.; Boulton, Andrew J.M.; Tavakoli, Mitra; Efron, Nathan; Malik, Rayaz A.

doi:10.1007/s00125-018-4653-8

Cited by 110 publications

(118 citation statements)

References 10 publications

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“…This non-invasive technique uses a combination of corneal nerve fiber length, nerve branch density, and nerve fiber density to evaluate the corneal nerve plexus 175176. It has been shown to detect early small nerve fiber damage in many disorders 175177178179180181182.…”

Section: Diagnostic Approachmentioning

confidence: 99%

“…There is only a modest correlation with disease stage in any patient and the correlation is of limited utility in clinical practice 183184185. A recent study of nearly 1000 patients with type 1 and type 2 diabetes demonstrated the diagnostic validity of corneal confocal microscopy using a 12.5 mm/mm 2 optimal threshold for automated corneal nerve fiber length in type 1 diabetes (73% sensitivity, 69% specificity) and a 12.3 mm/mm 2 optimal threshold in type 2 diabetes (69% sensitivity, 63% specificity) 176. When considering the entire cohort, a lower threshold for automated corneal nerve fiber length of 8.6 mm/mm 2 could rule in diabetic polyneuropathy and an upper threshold of 15.3 mm/mm 2 could rule it out (88% specificity, 88% sensitivity).…”

Section: Diagnostic Approachmentioning

confidence: 99%

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Diagnosis and management of sensory polyneuropathy

Gwathmey

Pearson

2019

BMJ

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Sensory polyneuropathies, which are caused by dysfunction of peripheral sensory nerve fibers, are a heterogeneous group of disorders that range from the common diabetic neuropathy to the rare sensory neuronopathies. The presenting symptoms, acuity, time course, severity, and subsequent morbidity vary and depend on the type of fiber that is affected and the underlying cause. Damage to small thinly myelinated and unmyelinated nerve fibers results in neuropathic pain, whereas damage to large myelinated sensory afferents results in proprioceptive deficits and ataxia. The causes of these disorders are diverse and include metabolic, toxic, infectious, inflammatory, autoimmune, and genetic conditions. Idiopathic sensory polyneuropathies are common although they should be considered a diagnosis of exclusion. The diagnostic evaluation involves electrophysiologic testing including nerve conduction studies, histopathologic analysis of nerve tissue, serum studies, and sometimes autonomic testing and cerebrospinal fluid analysis. The treatment of these diseases depends on the underlying cause and may include immunotherapy, mitigation of risk factors, symptomatic treatment, and gene therapy, such as the recently developed RNA interference and antisense oligonucleotide therapies for transthyretin familial amyloid polyneuropathy. Many of these disorders have no directed treatment, in which case management remains symptomatic and supportive. More research is needed into the underlying pathophysiology of nerve damage in these polyneuropathies to guide advances in treatment.

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Section: Diagnostic Approachmentioning

confidence: 99%

Section: Diagnostic Approachmentioning

confidence: 99%

Diagnosis and management of sensory polyneuropathy

Gwathmey

Pearson

2019

BMJ

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“…52 Future studies will aim to quantify morphologic parameters, such as nerval length and density, with the μOCT to compare them among healthy and diseased corneas because these parameters have been shown to be associated with nerve degeneration. 21 Furthermore, in vivo investigations using μOCT will potentially enable to study early onsets of nerval degeneration caused by ophthalmic as well as nonophthalmic diseases. [1][2][3][4][5] In conclusion, we have presented 3D μOCT corneal nerve imaging and tracking results.…”

Section: Discussionmentioning

confidence: 99%

Stromal Nerve Imaging and Tracking Using Micro-Optical Coherence Tomography

Elhardt

Wertheimer

Wartak

et al. 2020

Trans. Vis. Sci. Tech.

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Citation: Elhardt C, Wertheimer CM, Wartak A, Zhao J, Leung HM, Kassumeh SA, Yin B, Tearney GJ, Birngruber R. Stromal nerve imaging and tracking using micro-optical coherence tomography. Trans Vis Sci Tech. 2020;9(5):6, https://doi.org/10. 1167/tvst.9.5.6 Purpose: To image, track and map the nerve fiber distribution in excised rabbit corneas over the entire stromal thickness using micro-optical coherence tomography (μOCT) to develop a screening tool for early peripheral neuropathy.Methods: Excised rabbit corneas were consecutively imaged by a custom-designed μOCT prototype and a commercial laser scanning fluorescence confocal microscope. The μOCT images with a field of view of approximately 1 × 1 mm were recorded with axial and transverse resolutions of approximately 1 μm and approximately 4 μm, respectively. In the volumetric μOCT image data, network maps of hyper-reflective, branched structures traversing different stromal compartments were segmented using semiautomatic image processing algorithms. Furthermore, the same corneas received βIIItubulin antibody immunostaining before digital confocal microscopy, and a comparison between μOCT image data and immunohistochemistry analysis was performed to validate the nerval origin of the tracked network structures.Results: Semiautomatic tracing of the nerves with a high range of different thicknesses was possible through the whole corneal volumes, creating a skeleton of the traced nerves. There was a good conformity between the hyper-reflective structures in the μOCT data and the stained nerval structures in the immunohistochemistry data. Conclusions:This article demonstrates nerval imaging and tracking as well as a spatial correlation between μOCT and a fluorescence corneal nerve standard for larger nerves throughout the full thickness of the cornea ex vivo.Translational Relevance: Owing to its advantageous properties, μOCT may become useful as a noncontact method for assessing nerval structures in humans to screen for early peripheral neuropathy.

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“…Corneal nerve loss occurs in children with type 1 diabetes, subjects with IGT, and recently diagnosed type 2 diabetes and is associated with the severity of DN . It has good diagnostic performance for somatic and autonomic diabetic neuropathy and predicts the development of DN . Furthermore, in patients with type 1 diabetes undergoing simultaneous pancreas and kidney transplantation corneal nerve regeneration occurs within 6 months and is followed by an improvement in neuropathic symptoms and neurophysiology at 24 and 36 months, respectively …”

Section: Small Fibre Structurementioning

confidence: 99%

Diabetic neuropathy: A focus on small fibres

Malik

2019

Diabetes Metabolism Res

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Diabetic peripheral neuropathy (DPN) is diagnosed too late, which contrasts with our approach for diabetic retinopathy and nephropathy, where incipient disease is detected early enabling timely treatment. The 10‐g monofilament and a foot exam are the commonly used methods for screening diabetic neuropathy, but this primarily identifies moderate to severe diabetic neuropathy. Small fibres are damaged early and are associated with the development of painful diabetic neuropathy, foot ulceration, and Charcot foot. Tests of small fibre damage include thermal thresholds, microneurography, evoked potentials, sudomotor function, laser Doppler flare, skin biopsy, and corneal confocal microscopy. Measures of small fibre damage and repair may be key to the assessment of efficacy in clinical trials of disease modifying therapies for diabetic neuropathy.

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Corneal confocal microscopy for identification of diabetic sensorimotor polyneuropathy: a pooled multinational consortium study

Cited by 110 publications

References 10 publications

Diagnosis and management of sensory polyneuropathy

Diagnosis and management of sensory polyneuropathy

Stromal Nerve Imaging and Tracking Using Micro-Optical Coherence Tomography

Diabetic neuropathy: A focus on small fibres

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