scholarly journals Effect of treatment with exenatide and pioglitazone or basal-bolus insulin on diabetic neuropathy: a substudy of the Qatar Study

2020 ◽  
Vol 8 (1) ◽  
pp. e001420 ◽  
Author(s):  
Georgios Ponirakis ◽  
Muhammad A Abdul-Ghani ◽  
Amin Jayyousi ◽  
Hamad Almuhannadi ◽  
Ioannis N Petropoulos ◽  
...  
Keyword(s):  
Body Weight ◽  
Nerve Branch ◽  
Sudomotor Function ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerves ◽  
Corneal Nerve ◽  
Branch Density ◽  
Bolus Insulin ◽  
Basal Bolus ◽  
Vibration Perception

IntroductionTo assess the effect of exenatide and pioglitazone or basal-bolus insulin on diabetic peripheral neuropathy (DPN) in patients with poorly controlled type 2 diabetes (T2D).Research design and methodsThis is a substudy of the Qatar Study, an open-label, randomized controlled trial. 38 subjects with poorly controlled T2D were studied at baseline and 1-year follow-up and 18 control subjects were assessed at baseline only. A combination of exenatide (2 mg/week) and pioglitazone (30 mg/day) or glargine with aspart insulin were randomly assigned to patients to achieve an HbA1c <53 mmol/mol (<7%). DPN was assessed with corneal confocal microscopy (CCM), DN4, vibration perception and sudomotor function.ResultsSubjects with T2D had reduced corneal nerves, but other DPN measures were comparable with the control group. In the combination treatment arm (n=21), HbA1c decreased by 35.2 mmol/mol (3.8 %) (p<0.0001), body weight increased by 5.6 kg (p<0.0001), corneal nerve branch density increased (p<0.05), vibration perception worsened (p<0.05), and DN4 and sudomotor function showed no change. In the insulin treatment arm, HbA1c decreased by 28.7 mmol/mol (2.7 %) (p<0.0001), body weight increased by 4.6 kg (p<0.01), corneal nerve branch density and fiber length increased (p≤0.01), vibration perception improved (p<0.01), and DN4 and sudomotor function showed no change. There was no association between the change in CCM measures with change in HbA1c, weight or lipids.ConclusionsTreatment with exenatide and pioglitazone or basal-bolus insulin results in corneal nerve regeneration, but no change in neuropathic symptoms or sudomotor function over 1 year.

Distal Corneal Small Nerve Fibre Damage in Subjects With Obesity

2021 ◽  
Author(s):  
Zohaib Iqbal ◽  
Maryam Ferdousi ◽  
Alise Kalteniece ◽  
Safwaan Adam ◽  
Jan H. Ho ◽  
...  
Keyword(s):  
Nerve Fibre ◽  
Fibre Length ◽  
Relative Reduction ◽  
Symptom Profile ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerves ◽  
Obese Subjects ◽  
Corneal Nerve ◽  
Vibration Perception ◽  
Dying Back

Abstract Background: We have previously shown that subjects with obesity have elevated vibration and thermal perception thresholds and central corneal nerve loss and patients with diabetic neuropathy have greater corneal nerve loss at the inferior whorl compared to the central cornea. In the current study, we assessed whether there is evidence for a dying-back neuropathy in subjects with obesity with and without diabetes. Methods: 57 obese subjects, with and without diabetes (DM+, n=30; DM-, n=27 respectively) and age- and sex‑matched controls (n=21) underwent venous blood sampling and assessment of the neuropathy symptom profile (NSP), neuropathy disability score (NDS), vibration, cold and warm threshold testing, cardiac autonomic function, and corneal confocal microscopy (CCM).Results: NSP and NDS were significantly elevated in obese DM+ (p<0.0001; p=0.001) and DM- (p<0.0001; p=0.001) subjects compared to controls. Vibration perception threshold was significantly higher in DM+ (p=0.001), but not in DM- (p=0.06), compared to controls, whilst cold (p = 0.87) and warm (p = 0.52) perception thresholds did not differ between groups. Deep breathing heart rate variability was significantly lower in DM+ (p=0.01), but not DM- (p=0.9) subjects compared to controls. Corneal nerve fibre density [26.8 ±6.22 vs 26.8 ±6.01 vs 35.3 ±7.41, p<0.0001], branch density [55.4 ±28.2 vs 58.4 ±28.5 vs 88.2 ±31.1, p<0.001], fibre length (CNFL) [17.6 ±4.43 vs 19.9 ±5.43 vs 26.7 ±5.31, p <0.0001], inferior whorl length (IWL) [17.9 ±6.10 vs 18.6 ±7.42 vs 35.3 ±9.70, p<0.0001] and total nerve fibre length (TNFL) [35.5 ±9.58 vs 38.5 ±11.0 vs 62.0 ±12.3, p<0.0001] were significantly lower in obese subjects without and with diabetes compared to controls. In comparison to controls, there was a greater relative reduction in IWL compared to CNFL in DM+ (47.3% vs 25.5%) and DM- (49.3% vs 34.1%).Conclusion: We demonstrate evidence of peripheral neuropathy characterised by neuropathic symptoms, neurological deficits, elevated vibration perception and autonomic dysfunction with a dying-back neuropathy affecting the corneal nerves in obese subjects with and without type 2 diabetes.

scholarly journals Corneal confocal microscopy detects small fibre neurodegeneration in Parkinson's disease using automated analysis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sze Hway Lim ◽  
Maryam Ferdousi ◽  
Alise Kalteniece ◽  
Lewis Kass-Iliyya ◽  
Ioannis N. Petropoulos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Confocal Microscopy ◽  
Nerve Fibre ◽  
Fibre Length ◽  
Mean Difference ◽  
Nerve Branch ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve ◽  
Branch Density

AbstractWe studied the utility of corneal confocal microscopy (CCM) in detecting a reduction in corneal nerve parameters in a large cohort of patients with Parkinson’s disease (PD) compared to controls using a fully automated potentially scalable method of analysis. We also assessed if CCM parameters are related to the severity and sub-type of PD. 98 participants with PD and 26 healthy controls underwent CCM with automated corneal nerve quantification, MDS-UPDRS III, Hoehn and Yahr scale, Montreal Cognitive Assessment, Parkinson’s Disease Questionnaire-39 and PD subtype assessment. Corneal nerve fibre density (mean difference: − 5.00 no/mm2, 95% confidence interval (CI) [− 7.89, − 2.12], p = 0.001), corneal nerve branch density (mean difference: − 10.71 no/mm2, 95% CI [− 16.93, − 4.48], p = 0.003), corneal total branch density (mean difference: − 14.75 no/mm2, 95% CI [− 23.58, − 5.92], p = 0.002), and corneal nerve fibre length (mean difference: − 2.57 mm/mm2, 95% CI [− 4.02, − 1.12], p = 0.001) were significantly lower in PD participants compared to controls. There was no correlation between corneal nerve parameters and duration, severity or subtype of PD, cognitive function or quality of life. CCM with automated corneal nerve analysis identifies nerve fibre damage and may act as a biomarker for neurodegeneration in PD.

scholarly journals An In Vivo Confocal Microscopic Study of Corneal Nerve Morphology in Unilateral Keratoconus

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Natasha Kishore Pahuja ◽  
Rohit Shetty ◽  
Rudy M. M. A. Nuijts ◽  
Aarti Agrawal ◽  
Arkasubhra Ghosh ◽  
...  
Keyword(s):  
Nerve Fiber ◽  
Nerve Branch ◽  
Intergroup Comparison ◽  
Corneal Nerve ◽  
Group 3 ◽  
Group 2 ◽  
Branch Density ◽  
Corneal Nerve Morphology ◽  
Group 1

Purpose.To study the corneal nerve morphology and its importance in unilateral keratoconus.Materials and Methods.In this prospective cross-sectional study, 33 eyes of 33 patients with keratoconus in one eye (Group 3) were compared with the other normal eye of the same patients (Group 2) and 30 eyes of healthy patients (Group 1). All patients underwent detailed ophthalmic examination followed by topography with Pentacam HR and in vivo confocal microscopy (IVCM). Five images obtained with IVCM were analyzed using an automated CCmetrics software version 1.0 for changes in subbasal plexus of nerves.Results.Intergroup comparison showed statistically significant reduction in corneal nerve fiber density (CNFD) and length (CNFL) in Group 3 as compared to Group 1 (p<0.001andp=0.001, resp.) and Group 2 (p=0.01andp=0.02, resp.). Though corneal nerve fiber length, diameter, area, width, corneal nerve branch density, and corneal total branch density were found to be higher in decentered cones, only the corneal nerve branch density (CNBD) was found to be statistically significant (p<0.01) as compared to centered cones.Conclusion.Quantitative changes in the corneal nerve morphology can be used as an imaging marker for the early diagnosis of keratoconus before the onset of refractive or topography changes.

Clinical experiences with basal analogue insulin in routine care. Retrospective follow up analysis of a database from daily routine care

2013 ◽  
Vol 154 (37) ◽  
pp. 1476-1484
Author(s):  
Zsolt Sudár ◽  
Lajos Muth ◽  
Csaba Nyirati ◽  
Vince Szí ◽  
János Tornóczky ◽  
...  
Keyword(s):  
Body Weight ◽  
Metabolic Control ◽  
Human Insulin ◽  
Insulin Dose ◽  
Routine Care ◽  
Analogue Insulin ◽  
Bolus Insulin ◽  
Basal Bolus

Introduction: Basal-bolus insulin regime is frequently used in type 2 diabetes in order to improve metabolic control and decrease the risk of complications. A general question is, however, the effect of application of analogue insulin in comparison to human insulin regimes. Aim: The aim of the authors was to perform a retrospective database analysis among patients who were switched from human insulin only based basal-bolus regime to analogue only insulin regime in order to examine changes in metabolic control, body weight, insulin dose and basal:bolus insulin ratio. Method: Type 2 diabetic patients (n = 137) were enrolled who used once daily basal insulin with complementary bolus insulin given at main meals, and human insulin was switched to analogue insulin. Patients were divided into two groups using detemir (n = 103) or glargine (n = 34). Results: During 17 months ofanalogue insulin treatment the HbA1c was decreased by 0.34% (detemir –0.44%; glargine –0.17%). Body weight was increased by 1.11 kg (detemir +1.0 kg; glargine +1.43 kg). The basal:bolus insulin ratio increased in all groups (entire cohort 6.04%, detemir 5.26%, glargine 8.37%). The average insulin dose was 80.76 units at the end of follow up. There was no significant difference in terms of total and basal insulin doses between detemir (27.89 and 79.78 U, respectively) and glargine group (32.85 and 83.74 U, respectively). Conclusions: These results support that switching from human to analogue insulin in basal-bolus regime could improve the metabolic control by increasing dose of basal analogue insulin and basal: bolus ratio. Both detemir and glargine can provide similar improvement in metabolic control with the same insulin dose but with relatively more weight gain with glargine. Orv. Hetil., 2013, 154, 1476–1484.

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

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.

scholarly journals Comparing the results of manual and automated quantitative corneal neuroanalysing modules for beginners

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Po-Ying Wu ◽  
Jo-Hsuan Wu ◽  
Yi-Ting Hsieh ◽  
Lin Chih-Chieh Chen ◽  
Ting Cheng ◽  
...  
Keyword(s):  
Nerve Fiber ◽  
Correlation Coefficient ◽  
Intraclass Correlation ◽  
Fiber Density ◽  
Nerve Branch ◽  
Observer Reliability ◽  
Automated Method ◽  
Corneal Nerve ◽  
Branch Density

AbstractThis study aimed to evaluate the reliability of in vivo confocal microscopic neuroanalysis by beginners using manual and automated modules. Images of sub-basal corneal nerve plexus (SCNP) from 108 images of 18 healthy participants were analyzed by 7 beginner observers using manual (CCMetrics, [CCM]) and automated (ACCMetrics, [ACCM]) module. SCNP parameters analyzed included corneal nerve fiber density (NFD), corneal nerve branch density (NBD), corneal nerve fiber length (NFL), and tortuosity coefficient (TC). The intra-observer repeatability, inter-observer reliability, inter-module agreement, and left–right eye symmetry level of SCNP parameters were examined. All observers showed good intra-observer repeatability using CCM (intraclass correlation coefficient [ICC] > 0.60 for all), except when measuring TC. Two observers demonstrated especially excellent repeatability in analyzing NFD, NBD, and NFL using manual mode, indicating the quality of interpretation may still be observer-dependent. Among all SCNP parameters, NFL had the best inter-observer reliability (Spearman’s rank-sum correlation coefficient [SpCC] and ICC > 0.85 for the 3 original observers) and left–right symmetry level (SpCC and ICC > 0.60). In the additional analysis of inter-observer reliability using results by all 7 observers, only NFL showed good inter-observer reliability (ICC = 0.79). Compared with CCM measurements, values of ACCM measurements were significantly lower, implying a poor inter-module agreement. Our result suggested that performance of quantitative corneal neuroanalysis by beginners maybe acceptable, with NFL being the most reliable parameter, and automated method cannot fully replace manual work.

scholarly journals Corneal Nerve Loss in Patients With TIA and Acute Ischemic Stroke in Relation To Circulating Markers of Inflammation and Vascular Integrity

2021 ◽  
Author(s):  
Adnan Khan ◽  
Aijaz Parray ◽  
Naveed Akhtar ◽  
Abdelali Agouni ◽  
Saadat Kamran ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebrovascular Disease ◽  
Acute Ischemic Stroke ◽  
Nerve Fiber ◽  
Fiber Density ◽  
Nerve Branch ◽  
Vascular Integrity ◽  
Markers Of Inflammation ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

Abstract Background Vascular and inflammatory mechanisms are implicated in the development of cerebrovascular disease and corneal nerve loss occurs in patients with transient ischemic attack (TIA) and acute ischemic stroke (AIS). We have assessed whether serum markers of inflammation and vascular integrity are associated with the severity of corneal nerve loss in patients with TIA and AIS. Methods Corneal confocal microscopy (CCM) was performed to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL) in 105 patients with TIA or AIS and age matched control subjects (n=56). Circulating levels of IL-6, MMP-2, MMP-9, E-Selectin, P-Selectin and VEGF were quantified in patients within 48 hours of presentation with a TIA or AIS. Results CNFL (P=0.000, P=0.000), CNFD (P=0.122, P=0.000) and CNBD (P=0.002, P=0.000) were reduced in patients with TIA and AIS compared to controls, respectively with no difference between patients with AIS and TIA. The NIHSS Score (P=0.000), IL-6 (P=0.011) and E-Selectin (P=0.032) were higher in patients with AIS compared to TIA with no difference in MMP-2 (P=0.636), MMP-9 (P=0.098), P-Selectin (P=0.395) and VEGF (P=0.831). CNFL (r=0.218, P=0.026) and CNFD (r=0.230, P=0.019) correlated with IL-6 and multiple regression analysis showed a positive association of CNFL and CNFD with IL-6 (P=0.041, P=0.043). Conclusions Patients with TIA and stroke have evidence of corneal nerve loss and elevated IL6 and E-selectin levels. Larger longitudinal studies are required to determine the association between inflammatory and vascular markers and corneal nerve fiber loss in patients with cerebrovascular disease.

scholarly journals Artificial intelligence utilising corneal confocal microscopy for the diagnosis of peripheral neuropathy in diabetes mellitus and prediabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Frank G. Preston ◽  
Yanda Meng ◽  
Jamie Burgess ◽  
Maryam Ferdousi ◽  
Shazli Azmi ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Peripheral Neuropathy ◽  
Confocal Microscopy ◽  
Large Scale ◽  
Data Augmentation ◽  
Learning Algorithm ◽  
Deep Learning Algorithm ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerves ◽  
Corneal Nerve

Abstract Aims/hypothesis We aimed to develop an artificial intelligence (AI)-based deep learning algorithm (DLA) applying attribution methods without image segmentation to corneal confocal microscopy images and to accurately classify peripheral neuropathy (or lack of). Methods The AI-based DLA utilised convolutional neural networks with data augmentation to increase the algorithm’s generalisability. The algorithm was trained using a high-end graphics processor for 300 epochs on 329 corneal nerve images and tested on 40 images (1 image/participant). Participants consisted of healthy volunteer (HV) participants (n = 90) and participants with type 1 diabetes (n = 88), type 2 diabetes (n = 141) and prediabetes (n = 50) (defined as impaired fasting glucose, impaired glucose tolerance or a combination of both), and were classified into HV, those without neuropathy (PN−) (n = 149) and those with neuropathy (PN+) (n = 130). For the AI-based DLA, a modified residual neural network called ResNet-50 was developed and used to extract features from images and perform classification. The algorithm was tested on 40 participants (15 HV, 13 PN−, 12 PN+). Attribution methods gradient-weighted class activation mapping (Grad-CAM), Guided Grad-CAM and occlusion sensitivity displayed the areas within the image that had the greatest impact on the decision of the algorithm. Results The results were as follows: HV: recall of 1.0 (95% CI 1.0, 1.0), precision of 0.83 (95% CI 0.65, 1.0), F1-score of 0.91 (95% CI 0.79, 1.0); PN−: recall of 0.85 (95% CI 0.62, 1.0), precision of 0.92 (95% CI 0.73, 1.0), F1-score of 0.88 (95% CI 0.71, 1.0); PN+: recall of 0.83 (95% CI 0.58, 1.0), precision of 1.0 (95% CI 1.0, 1.0), F1-score of 0.91 (95% CI 0.74, 1.0). The features displayed by the attribution methods demonstrated more corneal nerves in HV, a reduction in corneal nerves for PN− and an absence of corneal nerves for PN+ images. Conclusions/interpretation We demonstrate promising results in the rapid classification of peripheral neuropathy using a single corneal image. A large-scale multicentre validation study is required to assess the utility of AI-based DLA in screening and diagnostic programmes for diabetic neuropathy. Graphical abstract

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