scholarly journals Corneal nerve loss as a surrogate marker for poor pial collaterals in patients with acute ischemic stroke

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adnan Khan ◽  
Ajay Menon ◽  
Naveed Akhtar ◽  
Saadat Kamran ◽  
Ahmad Muhammad ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endothelial Cell ◽  
Acute Ischemic Stroke ◽  
Nerve Fibre ◽  
Fibre Length ◽  
Surrogate Marker ◽  
Nerve Branch ◽  
Cell Parameters ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

AbstractIn patients with acute ischemic stroke, pial collaterals play a key role in limiting neurological disability by maintaining blood flow to ischemic penumbra. We hypothesized that patient with poor pial collaterals will have greater corneal nerve and endothelial cell abnormalities. In a cross-sectional study, 35 patients with acute ischemic stroke secondary to middle cerebral artery (MCA) occlusion with poor (n = 12) and moderate-good (n = 23) pial collaterals and 35 healthy controls underwent corneal confocal microscopy and quantification of corneal nerve and endothelial cell morphology. In patients with MCA stroke, corneal nerve fibre length (CNFL) (P < 0.001), corneal nerve fibre density (CNFD) (P = 0.025) and corneal nerve branch density (CNBD) (P = 0.002) were lower compared to controls. Age, BMI, cholesterol, triglycerides, HDL, LDL, systolic blood pressure, NIHSS and endothelial cell parameters did not differ but mRS was higher (p = 0.023) and CNFL (p = 0.026) and CNBD (p = 0.044) were lower in patients with poor compared to moderate-good collaterals. CNFL and CNBD distinguished subjects with poor from moderate-good pial collaterals with an AUC of 72% (95% CI 53–92%) and 71% (95% CI 53–90%), respectively. Corneal nerve loss is greater in patients with poor compared to moderate-good pial collaterals and may act as a surrogate marker for pial collateral status in patients with ischemic stroke.

scholarly journals Corneal Nerve Loss in Patients with Acute Ischemic Stroke: A Surrogate Marker for Poor Pial Collaterals

2021 ◽  
Author(s):  
Adnan Khan ◽  
Ajay Menon ◽  
Naveed Akhtar ◽  
Saadat Kamran ◽  
Ahmad Muhammad ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endothelial Cell ◽  
Acute Ischemic Stroke ◽  
Fibre Length ◽  
Surrogate Marker ◽  
Artery Occlusion ◽  
Cell Parameters ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve ◽  
Branch Density

Abstract Background: In patients with ischemic stroke, pial collaterals play a key role in limiting neurological disability by maintaining blood flow to ischemic penumbra. We hypothesized that patient with poor pial collateral status will have greater corneal nerve and endothelial cell abnormalities.Method: 35 patients with acute ischemic stroke secondary to middle cerebral artery occlusion with poor (n=12) and moderate/good (n=23) pial collaterals and 35 healthy controls underwent corneal confocal microscopy and quantification of corneal nerve and endothelial cell morphology.Results: In patients with MCA stroke, corneal nerve fibre length (CNFL) (P=0.000), density (CNFD) (P=0.025) and branch density (CNBD) (P=0.002) were lower compared to controls. Age, BMI, cholesterol, triglycerides, HDL, LDL, systolic blood pressure, NIHSS and endothelial cell parameters did not differ but mRS was higher (p=0.023) and CNFL (p=0.026) and CNBD (p=0.044) were lower in patients with poor compared to moderate-good collaterals. CNFL and CNBD distinguished subjects with poor from good pial collaterals with an AUC of 72% (95% CI: 53-92%) and 71% (95% CI: 53-90%), respectively. Conclusion: Corneal nerve loss is greater in patients with poor compared to good pial collaterals and may act as a surrogate marker for pial collateral status in patients with ischemic stroke.

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 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 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 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 Corneal Confocal Microscopy Detects Corneal Nerve Damage in Patients Admitted With Acute Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (11) ◽  
pp. 3012-3018 ◽  
Author(s):  
Adnan Khan ◽  
Naveed Akhtar ◽  
Saadat Kamran ◽  
Georgios Ponirakis ◽  
Ioannis N. Petropoulos ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Confocal Microscopy ◽  
Acute Ischemic Stroke ◽  
Nerve Damage ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

scholarly journals Diagnosis of neuropathy and risk factors for corneal nerve loss in type 1 and type 2 diabetes: A corneal confocal microscopy study

2020 ◽  
Author(s):  
Maryam Ferdousi ◽  
Alise Kalteniece ◽  
Shazli Azmi ◽  
Ioannis N Petropoulos ◽  
Georgios Ponirakis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Peripheral Neuropathy ◽  
Nerve Fibre ◽  
Fibre Length ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

<b>Purpose: </b>To assess the diagnostic utility of corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for corneal nerve loss. <p><b>Methods: </b>490 participants including 72 healthy controls, 149 with type 1 diabetes and 269 with type 2 diabetes underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors.</p> <p><b>Results: </b>Corneal nerve fibre density (CNFD) (P<0.0001, P<0.0001), branch density (CNBD) (P<0.0001, P<0.0001) and length (CNFL) (P<0.0001, P=0.02) were significantly lower in patients with type 1 and type 2 diabetes, compared to controls. CNFD (P<0.0001), CNBD (P<0.0001) and CNFL (P<0.0001) were lower in type 1 diabetes compared to type 2 diabetes. Receiver operating characteristics (ROC) curve analysis for the diagnosis of DPN demonstrated a good area under the curve (AUC) for CNFD=0.81, CNBD=0.74 and CNFL=0.73. Multivariable regression analysis showed a significant association between reduced corneal nerve fibre length with age (β=-0.27, P=0.007), HbA1c (β=-1.1, P=0.01) and weight (β=-0.14, P=0.03) in patients with type 2 diabetes and with duration of diabetes (β=-0.13, P=0.02), LDL cholesterol (β=1.8, P=0.04), and triglycerides (β=-2.87, P=0.009) in patients with type 1 diabetes. </p> <b>Conclusion: </b>CCM identifies more severe corneal nerve loss in patients with type 1 compared to type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in corneal nerve fibre length differ between type 1 and type 2 diabetes.

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 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 Diagnosis of neuropathy and risk factors for corneal nerve loss in type 1 and type 2 diabetes: A corneal confocal microscopy study

2020 ◽  
Author(s):  
Maryam Ferdousi ◽  
Alise Kalteniece ◽  
Shazli Azmi ◽  
Ioannis N Petropoulos ◽  
Georgios Ponirakis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Peripheral Neuropathy ◽  
Nerve Fibre ◽  
Fibre Length ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

<b>Purpose: </b>To assess the diagnostic utility of corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for corneal nerve loss. <p><b>Methods: </b>490 participants including 72 healthy controls, 149 with type 1 diabetes and 269 with type 2 diabetes underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors.</p> <p><b>Results: </b>Corneal nerve fibre density (CNFD) (P<0.0001, P<0.0001), branch density (CNBD) (P<0.0001, P<0.0001) and length (CNFL) (P<0.0001, P=0.02) were significantly lower in patients with type 1 and type 2 diabetes, compared to controls. CNFD (P<0.0001), CNBD (P<0.0001) and CNFL (P<0.0001) were lower in type 1 diabetes compared to type 2 diabetes. Receiver operating characteristics (ROC) curve analysis for the diagnosis of DPN demonstrated a good area under the curve (AUC) for CNFD=0.81, CNBD=0.74 and CNFL=0.73. Multivariable regression analysis showed a significant association between reduced corneal nerve fibre length with age (β=-0.27, P=0.007), HbA1c (β=-1.1, P=0.01) and weight (β=-0.14, P=0.03) in patients with type 2 diabetes and with duration of diabetes (β=-0.13, P=0.02), LDL cholesterol (β=1.8, P=0.04), and triglycerides (β=-2.87, P=0.009) in patients with type 1 diabetes. </p> <b>Conclusion: </b>CCM identifies more severe corneal nerve loss in patients with type 1 compared to type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in corneal nerve fibre length differ between type 1 and type 2 diabetes.

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