scholarly journals Diabetic Neuropathy Is Characterized by Progressive Corneal Nerve Fiber Loss in the Central and Inferior Whorl Regions

2020 ◽  
Vol 61 (3) ◽  
pp. 48 ◽  
Author(s):  
Maryam Ferdousi ◽  
Alise Kalteniece ◽  
Ioannis Petropoulos ◽  
Shazli Azmi ◽  
Shaishav Dhage ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Nerve Fiber ◽  
Corneal Nerve

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

2017 ◽  
Vol 31 (6) ◽  
pp. 1066-1073 ◽  
Author(s):  
Daniel Scarr ◽  
Leif E. Lovblom ◽  
Ilia Ostrovski ◽  
Dylan Kelly ◽  
Tong Wu ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Nerve Fiber ◽  
Fiber Length ◽  
Corneal Nerve

scholarly journals Early detection of diabetic neuropathy by investigating CNFL and IENFD in thy1-YFP mice

2016 ◽  
Vol 231 (2) ◽  
pp. 147-157 ◽  
Author(s):  
Janine Leckelt ◽  
Pedro Guimarães ◽  
Annett Kott ◽  
Alfredo Ruggeri ◽  
Oliver Stachs ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Nerve Fiber ◽  
Blood Glucose Concentration ◽  
Ex Vivo ◽  
Surrogate Marker ◽  
Nerve Fibers ◽  
Fiber Density ◽  
Corneal Confocal Microscopy ◽  
Intraepidermal Nerve Fiber Density ◽  
Corneal Nerve

Small fiber neuropathy is one of the most common and painful long-term complications of diabetes mellitus. Examination of the sub-basal corneal nerve plexus is a promising surrogate marker of diabetic neuropathy. To investigate the efficacy, reliability and reproducibility of in vivo corneal confocal microscopy (IVCCM), we used thy1-YFP mice, which express yellow fluorescence protein (YFP) in nerve fibers. 4 weeks after multiple low-dose injections of streptozotocin, thy1-YFP mice showed manifest diabetes. Subsequent application of insulin-releasing pellets for 8 weeks resulted in a significant reduction of blood glucose concentration and HbA1c, a significant increase in body weight and no further increase in advanced glycation end products (AGEs). IVCCM, carried out regularly over 12 weeks and analyzed both manually and automatically, revealed a significant loss of corneal nerve fiber length (CNFL) during diabetes manifestation and significant recovery after insulin therapy. Ex vivo analyses of CNFL by YFP-based microscopy confirmed the IVCCM results (with high sensitivity between manual and automated approaches) but demonstrated that the changes were restricted to the central cornea. Peripheral areas, not accessible by IVCCM in mice, remained virtually unaffected. Because parallel assessment of intraepidermal nerve fiber density revealed no changes, we conclude that IVCCM robustly captures early signs of diabetic neuropathy.

scholarly journals Corneal confocal microscopy compared with quantitative sensory testing and nerve conduction for diagnosing and stratifying the severity of diabetic peripheral neuropathy

2020 ◽  
Vol 8 (2) ◽  
pp. e001801
Author(s):  
Maryam Ferdousi ◽  
Alise Kalteniece ◽  
Shazli Azmi ◽  
Ioannis N Petropoulos ◽  
Anne Worthington ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Nerve Fiber ◽  
Nerve Conduction ◽  
Fiber Length ◽  
Quantitative Sensory Testing ◽  
Sensory Testing ◽  
Perception Threshold ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve ◽  
Vibration Perception

IntroductionDiabetic neuropathy can be diagnosed and assessed using a number of techniques including corneal confocal microscopy (CCM).Research design and methodsWe have undertaken quantitative sensory testing, nerve conduction studies and CCM in 143 patients with type 1 and type 2 diabetes without neuropathy (n=51), mild neuropathy (n=47) and moderate to severe neuropathy (n=45) and age-matched controls (n=30).ResultsVibration perception threshold (p<0.0001), warm perception threshold (WPT) (p<0.001), sural nerve conduction velocity (SNCV) (p<0.001), corneal nerve fiber density (CNFD) (p<0.0001), corneal nerve branch density (CNBD) (p<0.0001), corneal nerve fiber length (CNFL) (p=0.002), inferior whorl length (IWL) (p=0.0001) and average nerve fiber length (ANFL) (p=0.0001) showed a progressive abnormality with increasing severity of diabetic neuropathy. Receiver operating characteristic curve analysis for the diagnosis of diabetic neuropathy showed comparable performance in relation to the area under the curve (AUC) but differing sensitivities and specificities for vibration perception threshold (AUC 0.79, sensitivity 55%, specificity 90%), WPT (AUC 0.67, sensitivity 50%, specificity 76%), cold perception threshold (AUC 0.64, sensitivity 80%, specificity 47%), SNCV (AUC 0.70, sensitivity 76%, specificity 54%), CNFD (AUC 0.71, sensitivity 58%, specificity 83%), CNBD (AUC 0.70, sensitivity 69%, specificity 65%), CNFL (AUC 0.68, sensitivity 64%, specificity 67%), IWL (AUC 0.72, sensitivity 70%, specificity 65%) and ANFL (AUC 0.72, sensitivity 71%, specificity 66%).ConclusionThis study shows that CCM identifies early and progressive corneal nerve loss at the inferior whorl and central cornea and has comparable utility with quantitative sensory testing and nerve conduction in the diagnosis of diabetic neuropathy.

scholarly journals Rapid Corneal Nerve Fiber Loss: A Marker of Diabetic Neuropathy Onset and Progression

Diabetes Care ◽  
2020 ◽  
Vol 43 (8) ◽  
pp. 1829-1835 ◽  
Author(s):  
Evan J.H. Lewis ◽  
Leif E. Lovblom ◽  
Maryam Ferdousi ◽  
Elise M. Halpern ◽  
Maria Jeziorska ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Nerve Fiber ◽  
Corneal Nerve

scholarly journals Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology

2021 ◽  
Vol 2 ◽  
Author(s):  
Ioannis N. Petropoulos ◽  
Gulfidan Bitirgen ◽  
Maryam Ferdousi ◽  
Alise Kalteniece ◽  
Shazli Azmi ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Diabetic Neuropathy ◽  
Nerve Fiber ◽  
Clinical Intervention ◽  
Nerve Fibers ◽  
Fiber Density ◽  
Corneal Confocal Microscopy ◽  
Intraepidermal Nerve Fiber Density ◽  
Corneal Nerve ◽  
Small Nerve

Neuropathic pain has multiple etiologies, but a major feature is small fiber dysfunction or damage. Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that can image small nerve fibers in the cornea and has been utilized to show small nerve fiber loss in patients with diabetic and other neuropathies. CCM has comparable diagnostic utility to intraepidermal nerve fiber density for diabetic neuropathy, fibromyalgia and amyloid neuropathy and predicts the development of diabetic neuropathy. Moreover, in clinical intervention trials of patients with diabetic and sarcoid neuropathy, corneal nerve regeneration occurs early and precedes an improvement in symptoms and neurophysiology. Corneal nerve fiber loss also occurs and is associated with disease progression in multiple sclerosis, Parkinson's disease and dementia. We conclude that corneal confocal microscopy has good diagnostic and prognostic capability and fulfills the FDA criteria as a surrogate end point for clinical trials in peripheral and central neurodegenerative diseases.

Agreement Between Automated and Manual Quantification of Corneal Nerve Fiber Length: Implications for Diabetic Neuropathy Research

2015 ◽  
Vol 39 (6) ◽  
pp. 543-544
Author(s):  
Daniel Scarr ◽  
Ilia Ostrovski ◽  
Leif Erik Lovblom ◽  
Tong Wu ◽  
Elise M. Halpern ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Nerve Fiber ◽  
Fiber Length ◽  
Corneal Nerve

scholarly journals Corneal confocal microscopy differentiates inflammatory from diabetic neuropathy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Michael Fleischer ◽  
Inn Lee ◽  
Friedrich Erdlenbruch ◽  
Lena Hinrichs ◽  
Ioannis N. Petropoulos ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Confocal Microscopy ◽  
Diabetic Neuropathy ◽  
Nerve Fiber ◽  
Cell Density ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Basal Layer ◽  
Nerve Fibers ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

Abstract Background Immune-mediated neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP) are treatable neuropathies. Among individuals with diabetic neuropathy, it remains a challenge to identify those individuals who develop CIDP. Corneal confocal microscopy (CCM) has been shown to detect corneal nerve fiber loss and cellular infiltrates in the sub-basal layer of the cornea. The objective of the study was to determine whether CCM can distinguish diabetic neuropathy from CIDP and whether CCM can detect CIDP in persons with coexisting diabetes. Methods In this multicenter, case-control study, participants with CIDP (n = 55) with (n = 10) and without (n = 45) diabetes; participants with diabetes (n = 58) with (n = 28) and without (n = 30) diabetic neuropathy, and healthy controls (n = 58) underwent CCM. Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), and dendritic and non-dendritic cell density, with or without nerve fiber contact were quantified. Results Dendritic cell density in proximity to corneal nerve fibers was significantly higher in participants with CIDP with and without diabetes compared to participants with diabetic neuropathy and controls. CNFD, CNFL, and CNBD were equally reduced in participants with CIDP, diabetic neuropathy, and CIDP with diabetes. Conclusions An increase in dendritic cell density identifies persons with CIDP. CCM may, therefore, be useful to differentiate inflammatory from non-inflammatory diabetic neuropathy.

scholarly journals Association of corneal nerve fiber measures with cognitive function in dementia

2019 ◽  
Vol 6 (4) ◽  
pp. 689-697 ◽  
Author(s):  
Georgios Ponirakis ◽  
Hanadi Al Hamad ◽  
Anoop Sankaranarayanan ◽  
Adnan Khan ◽  
Mani Chandran ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Nerve Fiber ◽  
Corneal Nerve
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