scholarly journals Corneal confocal microscopy identifies small fibre damage and progression of diabetic neuropathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shaishav Dhage ◽  
Maryam Ferdousi ◽  
Safwaan Adam ◽  
Jan Hoong Ho ◽  
Alise Kalteniece ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Diabetic Neuropathy ◽  
Nerve Fibre ◽  
Fibre Length ◽  
Autonomic Nerve ◽  
Perception Threshold ◽  
Fibre Density ◽  
Symptom Profile ◽  
Corneal Confocal Microscopy ◽  
Patients With Diabetes

AbstractAccurately quantifying the progression of diabetic peripheral neuropathy is key to identify individuals who will progress to foot ulceration and to power clinical intervention trials. We have undertaken detailed neuropathy phenotyping to assess the longitudinal utility of different measures of neuropathy in patients with diabetes. Nineteen patients with diabetes (age 52.5 ± 14.7 years, duration of diabetes 26.0 ± 13.8 years) and 19 healthy controls underwent assessment of symptoms and signs of neuropathy, quantitative sensory testing, autonomic nerve function, neurophysiology, intra-epidermal nerve fibre density (IENFD) and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), branch density (CNBD) and fibre length (CNFL). Mean follow-up was 6.5 years. Glycated haemoglobin (p = 0.04), low-density lipoprotein-cholesterol (LDL-C) (p = 0.0009) and urinary albumin creatinine ratio (p < 0.0001) improved. Neuropathy symptom profile (p = 0.03), neuropathy disability score (p = 0.04), vibration perception threshold (p = 0.02), cold perception threshold (p = 0.006), CNFD (p = 0.03), CNBD (p < 0.0001), CNFL (p < 0.0001), IENFD (p = 0.04), sural (p = 0.02) and peroneal motor nerve conduction velocity (p = 0.03) deteriorated significantly. Change (∆) in CNFL correlated with ∆CPT (p = 0.006) and ∆Expiration/Inspiration ratio (p = 0.002) and ∆IENFD correlated with ∆CNFD (p = 0.005), ∆CNBD (p = 0.02) and ∆CNFL (p = 0.01). This study shows worsening of diabetic neuropathy across a range of neuropathy measures, especially CCM, despite an improvement in HbA1c and LDL-C. It further supports the utility of CCM as a rapid, non-invasive surrogate measure of diabetic neuropathy.

scholarly journals An artificial intelligence-based deep learning algorithm for the diagnosis of diabetic neuropathy using corneal confocal microscopy: a development and validation study

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 419-430 ◽  
Author(s):  
Bryan M. Williams ◽  
Davide Borroni ◽  
Rongjun Liu ◽  
Yitian Zhao ◽  
Jiong Zhang ◽  
...  
Keyword(s):  
Deep Learning ◽  
Confocal Microscopy ◽  
Diabetic Neuropathy ◽  
Nerve Fibre ◽  
Learning Algorithm ◽  
Fibre Length ◽  
Branch Points ◽  
Deep Learning Algorithm ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

Abstract Aims/hypothesis Corneal confocal microscopy is a rapid non-invasive ophthalmic imaging technique that identifies peripheral and central neurodegenerative disease. Quantification of corneal sub-basal nerve plexus morphology, however, requires either time-consuming manual annotation or a less-sensitive automated image analysis approach. We aimed to develop and validate an artificial intelligence-based, deep learning algorithm for the quantification of nerve fibre properties relevant to the diagnosis of diabetic neuropathy and to compare it with a validated automated analysis program, ACCMetrics. Methods Our deep learning algorithm, which employs a convolutional neural network with data augmentation, was developed for the automated quantification of the corneal sub-basal nerve plexus for the diagnosis of diabetic neuropathy. The algorithm was trained using a high-end graphics processor unit on 1698 corneal confocal microscopy images; for external validation, it was further tested on 2137 images. The algorithm was developed to identify total nerve fibre length, branch points, tail points, number and length of nerve segments, and fractal numbers. Sensitivity analyses were undertaken to determine the AUC for ACCMetrics and our algorithm for the diagnosis of diabetic neuropathy. Results The intraclass correlation coefficients for our algorithm were superior to those for ACCMetrics for total corneal nerve fibre length (0.933 vs 0.825), mean length per segment (0.656 vs 0.325), number of branch points (0.891 vs 0.570), number of tail points (0.623 vs 0.257), number of nerve segments (0.878 vs 0.504) and fractals (0.927 vs 0.758). In addition, our proposed algorithm achieved an AUC of 0.83, specificity of 0.87 and sensitivity of 0.68 for the classification of participants without (n = 90) and with (n = 132) neuropathy (defined by the Toronto criteria). Conclusions/interpretation These results demonstrated that our deep learning algorithm provides rapid and excellent localisation performance for the quantification of corneal nerve biomarkers. This model has potential for adoption into clinical screening programmes for diabetic neuropathy. Data availability The publicly shared cornea nerve dataset (dataset 1) is available at http://bioimlab.dei.unipd.it/Corneal%20Nerve%20Tortuosity%20Data%20Set.htm and http://bioimlab.dei.unipd.it/Corneal%20Nerve%20Data%20Set.htm.

scholarly journals Diagnostic utility of corneal confocal microscopy and intra-epidermal nerve fibre density in diabetic neuropathy

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0180175 ◽  
Author(s):  
Uazman Alam ◽  
Maria Jeziorska ◽  
Ioannis N. Petropoulos ◽  
Omar Asghar ◽  
Hassan Fadavi ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Diabetic Neuropathy ◽  
Nerve Fibre ◽  
Diagnostic Utility ◽  
Fibre Density ◽  
Corneal Confocal Microscopy

scholarly journals Corneal Confocal Microscopy – A Novel, Noninvasive Method to Assess Diabetic Peripheral Neuropathy

2014 ◽  
Vol 21 (4) ◽  
pp. 319-326 ◽  
Author(s):  
Georgeta Inceu ◽  
Horea Demea ◽  
Ioan Andrei Veresiu
Keyword(s):  
Peripheral Neuropathy ◽  
Confocal Microscopy ◽  
Diabetic Neuropathy ◽  
Diabetic Peripheral Neuropathy ◽  
Diabetic Patients ◽  
Noninvasive Method ◽  
Anthropometric Parameters ◽  
Perception Threshold ◽  
Peripheral Diabetic Neuropathy ◽  
Corneal Confocal Microscopy

AbstractBackground and aims. This article aims to compare corneal confocal microscopy (CCM) with acknowledged tests of diabetic peripheral neuropathy (DPN), to assess corneal nerve morphology using CCM in diabetic patients, and to underline possible correlations between clinical and biological parameters, diabetes duration and DPN severity. Material and methods. A total of 90 patients with type 2 diabetes were included in the study for whom we measured anthropometric parameters and we performed laboratory measurements (tests). The patients were assessed for diabetic peripheral neuropathy using Semmes-Weinstein Monofilament Testing (SWMT), Rapid-Current Perception Threshold (R-CPT) measurements using the Neurometer®, and CCM. We stratified the patients according to DPN severity, based on four parameters extracted after image analysis. Results. A higher percentage of patients were diagnosed with DPN using CCM (88.8%), compared with SWMT and R-CPT measurement (17.8% and 40% respectively). The incidence of DPN detected with CCM was considerable in patients with normal protective sensation and with normal R-CPT values. Conclusions. Our study showed that corneal confocal microscopy is a useful noninvasive method for diabetic neuropathy assessement in early stages. It was proven to directly quantify small fiber pathology, and to stratify neuropathic severity, and therefore can be used as a new, reliable tool in the diagnosis, clinical evaluation, and follow-up of peripheral 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.

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 nerve fibre damage in patients with painful diabetic neuropathy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alise Kalteniece ◽  
Maryam Ferdousi ◽  
Shazli Azmi ◽  
Womba M. Mubita ◽  
Andrew Marshall ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Diabetic Neuropathy ◽  
Nerve Fibre ◽  
Painful Diabetic Neuropathy ◽  
Corneal Confocal Microscopy ◽  
Small Nerve

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 In Vivo Confocal Microscopy Evaluation in Patients with Keratoconus

2022 ◽  
Vol 11 (2) ◽  
pp. 393
Author(s):  
Alvin Wei Jun Teo ◽  
Hassan Mansoor ◽  
Nigel Sim ◽  
Molly Tzu-Yu Lin ◽  
Yu-Chi Liu
Keyword(s):  
Confocal Microscopy ◽  
Nerve Regeneration ◽  
Nerve Fibre ◽  
Ex Vivo ◽  
Fibre Length ◽  
In Vivo Confocal Microscopy ◽  
Corneal Sensitivity ◽  
Mechanical Removal ◽  
Cellular Changes

Keratoconus is the most common primary corneal ectasia characterized by progressive focal thinning. Patients experience increased irregular astigmatism, decreased visual acuity and corneal sensitivity. Corneal collagen crosslinking (CXL), a minimally invasive procedure, is effective in halting disease progression. Historically, keratoconus research was confined to ex vivo settings. In vivo confocal microscopy (IVCM) has been used to examine the corneal microstructure clinically. In this review, we discuss keratoconus cellular changes evaluated by IVCM before and after CXL. Cellular changes before CXL include decreased keratocyte and nerve densities, disorganized subbasal nerves with thickening, increased nerve tortuosity and shortened nerve fibre length. Repopulation of keratocytes occurs up to 1 year post procedure. IVCM also correlates corneal nerve status to functional corneal sensitivity. Immediately after CXL, there is reduced nerve density and keratocyte absence due to mechanical removal of the epithelium and CXL effect. Nerve regeneration begins after 1 month, with nerve fibre densities recovering to pre-operative levels between 6 months to 1 year and remains stable up to 5 years. Nerves remain tortuous and nerve densities are reduced. Corneal sensitivity is reduced immediately postoperatively but recovers with nerve regeneration. Our article provides comprehensive review on the use of IVCM imaging in keratoconus patients.

Bilateral morphometric analysis of corneal sub-basal nerve plexus in patients undergoing unilateral cataract surgery: a preliminary in vivo confocal microscopy study

2020 ◽  
pp. bjophthalmol-2019-315449 ◽  
Author(s):  
Giuseppe Giannaccare ◽  
Federico Bernabei ◽  
Marco Pellegrini ◽  
Fabio Guaraldi ◽  
Federica Turchi ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Cataract Surgery ◽  
Nerve Fibre ◽  
Fibre Length ◽  
Nerve Plexus ◽  
In Vivo Confocal Microscopy ◽  
Corneal Nerve ◽  
Branch Density ◽  
Unilateral Cataract

AimsTo evaluate bilateral morphometric changes of corneal sub-basal nerve plexus (CSNP) occurring after unilateral cataract surgery by in vivo confocal microscopy (IVCM) images analysed with automated software.MethodsIVCM was performed before (V0) and 1 month after surgery (V1) in both operated eyes (OEs) and unoperated eyes (UEs) of 30 patients. Thirty age and sex-matched subjects acted as controls. Corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), corneal nerve total branch density (CTBD), corneal nerve fibre area (CNFA), corneal nerve fibre width, corneal nerve fractal dimension (CNFrD) and dendritic cells density were calculated.ResultsMean CNFD, CNBD, CNFL, CTBD, CNFA and CNFrD significantly decreased at V1 versus V0 in both eyes (respectively, 15.35±7.00 vs 21.21±6.56 n/mm2 in OEs and 20.11±6.69 vs 23.20±7.26 in UEs; 13.57±12.16 vs 26.79±16.91 n/mm2 in OEs and 24.28±14.88 vs 29.76±15.25 in UEs; 9.67±3.44 mm/mm2 vs 13.49±3.42 in OEs and 12.53±3.60 vs 14.02±3.82 in UEs; 22.81±18.77 vs 42.25±24.64 n/mm2 in OEs and 38.06±20.52 vs 43.93±22.27 in UEs; 0.0040±0.0021 vs 0.0058±0.0020 mm2/mm2 in OEs and 0.0049±0.0016 vs 0.0057±0.0019 in UEs; 1.418±0.058 vs 1.470±0.037 in OEs and 1.466±0.040 vs 1.477±0.036 in UEs; always p<0.049).ConclusionPatients undergoing cataract surgery exhibit bilateral alterations of CSNP. This finding could have broad implications in the setting of sequential cataract surgery.

Sign in / Sign up

Export Citation Format

Share Document