Agreement between automated and manual quantification of corneal nerve fiber length: Implications for diabetic neuropathy research

Scarr, Daniel; Lovblom, Leif E.; Ostrovski, Ilia; Kelly, Dylan; Wu, Tong; Farooqi, Mohammed A.; Halpern, Elise M.; Ngo, Mylan; Ng, Eduardo; Orszag, Andrej; Bril, Vera; Perkins, Bruce A.

doi:10.1016/j.jdiacomp.2016.07.024

Cited by 27 publications

(19 citation statements)

References 37 publications

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“… 14 , 21 , 22 , 47 Automated subbasal corneal nerve image analysis allows rapid quantification of corneal nerve fiber degeneration, 20 , 21 , 49 with comparable diagnostic efficiency to manual quantification. 50 Previous reviews have highlighted the extensive diabetes-related complications in the cornea 51 – 53 and have also shown that corneal nerve loss occurs in patients without diabetic retinopathy and significantly worsens in those with diabetic retinopathy. 54 – 56 Moreover, we have also recently shown that a reduction in corneal nerve fiber length predicts worsening of diabetic retinopathy.…”

Section: Discussionmentioning

confidence: 99%

Corneal Nerve Fractal Dimension: A Novel Corneal Nerve Metric for the Diagnosis of Diabetic Sensorimotor Polyneuropathy

Chen

Graham

Petropoulos

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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ObjectiveCorneal confocal microscopy (CCM), an in vivo ophthalmic imaging modality, is a noninvasive and objective imaging biomarker for identifying small nerve fiber damage. We have evaluated the diagnostic performance of previously established CCM parameters to a novel automated measure of corneal nerve complexity called the corneal nerve fiber fractal dimension (ACNFrD).MethodsA total of 176 subjects (84 controls and 92 patients with type 1 diabetes) with and without diabetic sensorimotor polyneuropathy (DSPN) underwent CCM. Fractal dimension analysis was performed on CCM images using purpose-built corneal nerve analysis software, and compared with previously established manual and automated corneal nerve fiber measurements.ResultsManual and automated subbasal corneal nerve fiber density (CNFD) (P < 0.0001), length (CNFL) (P < 0.0001), branch density (CNBD) (P < 0.05), and ACNFrD (P < 0.0001) were significantly reduced in patients with DSPN compared to patients without DSPN. The areas under the receiver operating characteristic curves for identifying DSPN were comparable: 0.77 for automated CNFD, 0.74 for automated CNFL, 0.69 for automated CNBD, and 0.74 for automated ACNFrD.ConclusionsACNFrD shows comparable diagnostic efficiency to identify diabetic patients with and without DSPN.

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Section: Discussionmentioning

confidence: 99%

Corneal Nerve Fractal Dimension: A Novel Corneal Nerve Metric for the Diagnosis of Diabetic Sensorimotor Polyneuropathy

Chen

Graham

Petropoulos

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…This technique has advantages over skin biopsy as it is rapid and non-invasive, but it is not yet widely available. 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.…”

Section: Diagnostic Approachmentioning

confidence: 99%

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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“…We, and others have shown that CCM can be used to detect early corneal nerve alterations [ 80 93 ] with excellent reproducibility between examiners, occasions and quantification methods ( Fig. 1 ) [ 94 95 96 97 98 ]. We have established a multinational normative reference database for corneal nerve morphology [ 99 ] and shown that healthy individuals exhibit morphometric stability over time [ 100 ].…”

Section: Corneal Confocal Microscopymentioning

confidence: 99%

Diagnosing Diabetic Neuropathy: Something Old, Something New

et al. 2018

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There are potentially many ways of assessing diabetic peripheral neuropathy (DPN). However, they do not fulfill U.S. Food and Drug Administration (FDA) requirements in relation to their capacity to assess therapeutic benefit in clinical trials of DPN. Over the past several decades symptoms and signs, quantitative sensory and electrodiagnostic testing have been strongly endorsed, but have consistently failed as surrogate end points in clinical trials. Therefore, there is an unmet need for reliable biomarkers to capture the onset and progression and to facilitate drug discovery in DPN. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging modality for in vivo evaluation of sensory C-fibers. An increasing body of evidence from multiple centers worldwide suggests that CCM fulfills the FDA criteria as a surrogate endpoint of DPN.

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Agreement between automated and manual quantification of corneal nerve fiber length: Implications for diabetic neuropathy research

Cited by 27 publications

References 37 publications

Corneal Nerve Fractal Dimension: A Novel Corneal Nerve Metric for the Diagnosis of Diabetic Sensorimotor Polyneuropathy

Corneal Nerve Fractal Dimension: A Novel Corneal Nerve Metric for the Diagnosis of Diabetic Sensorimotor Polyneuropathy

Diagnosis and management of sensory polyneuropathy

Diagnosing Diabetic Neuropathy: Something Old, Something New

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