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Rayaz A Malik - One of the best experts on this subject based on the ideXlab platform.

  • Corneal confocal microscopy identifies Corneal Nerve fibre loss and increased dendritic cells in patients with long covid
    British Journal of Ophthalmology, 2021
    Co-Authors: Gulfidan Bitirgen, Georgios Ponirakis, Rayaz A Malik, Ahmet Ozkagnici, Celalettin Korkmaz, Adil Zamani, Nazmi Zengin
    Abstract:

    Background/Aims Long 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. Methods Forty 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. Results The 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). Conclusion Corneal 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.

  • Corneal confocal microscopy demonstrates Corneal Nerve loss in patients with trigeminal neuralgia
    Frontiers in Neurology, 2020
    Co-Authors: Johnih Lee, Rayaz A Malik, Theresa Bocking, Dagny Hollelee, Bernd C Kieseier, Hanspeter Hartung, R F Guthoff, Christoph Kleinschnitz, Mark Stettner
    Abstract:

    Background: The diagnosis of trigeminal neuralgia (TN) is challenging due to the lack of objective diagnostics. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique, which allows quantification of Corneal Nerve fibers arising from the trigeminal ganglion and may allow the assessment of neurodegeneration in TN. Methods: CCM was undertaken in 11 patients with TN and 11 age-matched healthy controls. Corneal Nerve fiber density (CNFD), Corneal Nerve branch density, Corneal Nerve fiber length (CNFL), Corneal Nerve fiber width, Corneal Nerve fiber area, and dendritic cell and non-dendritic cell density with or without Nerve fiber contact were quantified. Results: Patients with TN had significantly lower CNFD and CNFL but no difference for any other Corneal Nerve or dendritic cell parameter in the ipsilateral and the contralateral cornea compared to the control group. There was no significant difference in Corneal Nerve and cell parameters between patients with TN with and without involvement of the ophthalmic Nerve (V1) or with Nerve vessel conflict. Conclusion: Corneal confocal microscopy is a rapid non-invasive imaging technique that identifies symmetrical Corneal Nerve loss in patients with TN.

  • early Corneal Nerve fibre damage and increased langerhans cell density in children with type 1 diabetes mellitus
    Scientific Reports, 2019
    Co-Authors: Maryam Ferdousi, Rayaz A Malik, Kenneth Romanchuk, Heidi Virtanen, Christine Millar, Danièle Pacaud
    Abstract:

    Corneal confocal microscopy (CCM) has been used to identify Corneal Nerve damage and increased Langerhans cell (LC) density in adults with Type 1 diabetes mellitus (T1DM). The purpose of this study was to evaluate whether Corneal confocal microscopy can identify early Corneal Nerve damage and change in LC density in children and adolescents with T1DM. 64 participants with T1DM (age-14.6 ± 2.5 years, duration of diabetes-9.1 ± 2.7 years, HbA1c-75.66 ± 2.53 mmol/mol [9.1 ± 1.8%]) and 48 age-matched healthy control subjects underwent CCM. Sub-basal Corneal Nerve morphology and the density of mature and immature LCs was quantified. Corneal Nerve fibre length and branch density were lower, whilst fibre density and tortuosity did not differ and both immature and mature LC density was significantly higher in T1DM compared to control subjects. There was no association between HbA1c and duration of diabetes with Nerve fibre parameters or LC’s density. Children and adolescents with T1DM demonstrate early immune activation and Nerve degeneration.

  • no relation between the severity of Corneal Nerve epithelial and keratocyte cell morphology with measures of dry eye disease in type 1 diabetes
    Investigative Ophthalmology & Visual Science, 2018
    Co-Authors: Maryam Ferdousi, Georgios Ponirakis, Ioannis N. Petropoulos, Alise Kalteniece, Shazli Azmi, Handrean Soran, Rayaz A Malik, Nathan Efron
    Abstract:

    Purpose: Patients with diabetes have a propensity to develop dry eye symptoms (DES), with reduced tear secretion and Corneal sensitivity. The underlying pathologic basis of DES was explored in patients with Type 1 diabetes. Methods: Forty-two patients with Type 1 diabetes mellitus (T1DM) (age: 49.21 ± 2.53 years, duration of diabetes: 29.98 ± 2.64 years) and 25 control subjects (age: 48.70 ± 2.84 years) underwent assessment of DES using a validated dry eye questionnaire, and tear stability and tear production were assessed using tear breakup time (TBUT) and Schirmer's test, respectively. Corneal confocal microscopy was undertaken to quantify Corneal Nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), keratocyte density (KD), and Corneal epithelial basal cell (CEBC) density and area. Results: The prevalence of DES was significantly higher (P = 0.03), and TBUT (P = 0.006), Corneal sensation (P < 0.0001), CNFD (P = 0.001), CNBD (P = 0.001), CNFL (P = 0.003), and KD (P = 0.04) were significantly lower in patients with T1DM compared to control subjects. However, these measures did not differ significantly between T1DM patients with and without dry eye. There was no correlation between DES and TBUT or Corneal Nerve keratocyte and CEBC morphology. Conclusions: DES and TBUT are significantly increased in patients with T1DM, but are not related to Corneal Nerve, basal epithelial, or keratocyte cell morphology.

  • Corneal confocal microscopy detects Corneal Nerve damage and increased dendritic cells in fabry disease
    Scientific Reports, 2018
    Co-Authors: Gulfidan Bitirgen, Rayaz A Malik, Ahmet Ozkagnici, Kultigin Turkmen, Nazmi Zengin
    Abstract:

    Fabry disease is characterised by neuropathic pain and accelerated vascular disease. This study evaluates the utility of Corneal confocal microscopy (CCM) to non-invasively quantify Corneal Nerve and endothelial cell morphology and dendritic cell (DC) density in relation to disease severity in subjects with Fabry disease. Seventeen consecutive participants with Fabry disease and 17 healthy control subjects were included in this cross-sectional study. Fabry disease severity was measured using the Mainz Severity Score Index (MSSI). Central Corneal sensitivity was assessed with a contact Corneal esthesiometer. There was a significant reduction in the Corneal sensitivity (5.75 [5.25–6.00] vs. 6.00 [6.00-6.00] cm, P = 0.014), Nerve fiber density (NFD) (26.4 ± 10.1 vs. 33.7 ± 7.9 fibers/mm2, P = 0.025) and Nerve fiber length (NFL) (15.9 ± 3.4 vs. 19.5 ± 4.4 mm/mm2, P = 0.012) and an increase in DC density (38.3 [17.5–97.3] vs. 13.5 [0–29.4] cells/mm2, P = 0.004) in subjects with Fabry disease compared to the healthy control subjects. The total MSSI score correlated with NFD (ρ = −0.686; P = 0.006), NFL (ρ = −0.692; P = 0.006), endothelial cell density (ρ = −0.511; P = 0.036), endothelial cell area (ρ = 0.514; P = 0.036) and α-galactosidase A enzyme activity (ρ = −0.723; P = 0.008). This study demonstrates reduced Corneal sensitivity, Corneal Nerve fiber damage and increased DCs in subjects with Fabry disease.

Ioannis N. Petropoulos - One of the best experts on this subject based on the ideXlab platform.

  • insulin resistance limits Corneal Nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control
    Journal of Diabetes Investigation, 2021
    Co-Authors: Georgios Ponirakis, Ioannis N. Petropoulos, Hamad Almuhannadi, Muhammad A Abdulghani, Amin Jayyousi, Mahmoud Zirie, Salma Almohannadi, Adnan Khan
    Abstract:

    AIMS/INTRODUCTION This study aimed to investigate whether insulin resistance (IR) in individuals with type 2 diabetes undergoing intensive glycemic control determines the extent of improvement in neuropathy. MATERIALS AND METHODS This was an exploratory substudy of an open-label, randomized controlled trial of individuals with poorly controlled type 2 diabetes treated with exenatide and pioglitazone or insulin to achieve a glycated hemoglobin <7.0% (<53 mmol/mol). Baseline IR was defined using homeostasis model assessment of IR, and change in neuropathy was assessed using Corneal confocal microscopy. RESULTS A total of 38 individuals with type 2 diabetes aged 50.2 ± 8.5 years with (n = 25, 66%) and without (n = 13, 34%) IR were studied. There was a significant decrease in glycated hemoglobin (P < 0.0001), diastolic blood pressure (P < 0.0001), total cholesterol (P < 0.01) and low-density lipoprotein (P = 0.05), and an increase in bodyweight (P < 0.0001) with treatment. Individuals with homeostasis model assessment of IR <1.9 showed a significant increase in Corneal Nerve fiber density (P ≤ 0.01), length (P ≤ 0.01) and branch density (P ≤ 0.01), whereas individuals with homeostasis model assessment of IR ≥1.9 showed no change. IR was negatively associated with change in Corneal Nerve fiber density after adjusting for change in bodyweight (P < 0.05). CONCLUSIONS Nerve regeneration might be limited in individuals with type 2 diabetes and IR undergoing treatment with pioglitazone plus exenatide or insulin to improve glycemic control.

  • diagnosis of neuropathy and risk factors for Corneal Nerve loss in type 1 and type 2 diabetes a Corneal confocal microscopy study
    Diabetes Care, 2021
    Co-Authors: Maryam Ferdousi, Georgios Ponirakis, Ioannis N. Petropoulos, Omar Asghar, Uazman Alam, Alise Kalteniece, Shazli Azmi, Andrew Marshall, Catherine Fullwood
    Abstract:

    OBJECTIVE To assess the diagnostic utility of Corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for Corneal Nerve loss. RESEARCH DESIGN AND METHODS A total of 490 participants, including 72 healthy control subjects, 149 with type 1 diabetes, and 269 with type 2 diabetes, underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors. RESULTS Corneal Nerve fiber density (CNFD) (P CONCLUSIONS CCM identifies more severe Corneal Nerve loss in patients with type 1 compared with type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in Corneal Nerve fiber length differ between type 1 and type 2 diabetes.

  • Corneal confocal microscopy compared with quantitative sensory testing and Nerve conduction for diagnosing and stratifying the severity of diabetic peripheral neuropathy
    BMJ open diabetes research & care, 2020
    Co-Authors: Maryam Ferdousi, Georgios Ponirakis, Ioannis N. Petropoulos, Uazman Alam, Alise Kalteniece, Shazli Azmi, Anne Worthington, Luca Donofrio, Shaishav Dhage, Andrew Marshall
    Abstract:

    INTRODUCTION Diabetic neuropathy can be diagnosed and assessed using a number of techniques including Corneal confocal microscopy (CCM). RESEARCH DESIGN AND METHODS We 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). RESULTS Vibration 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%). CONCLUSION This 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.

  • Corneal Nerve loss in children with type 1 diabetes mellitus without retinopathy or microalbuminuria
    Journal of Diabetes Investigation, 2020
    Co-Authors: Hoda Gad, Georgios Ponirakis, Ioannis N. Petropoulos, Adnan Khan, Bara Aljarrah, Saras Saraswathi, Parul Singh, Souhaila Al Khodor, Mamoun Elawad, Wesam Almasri
    Abstract:

    AIMS/INTRODUCTION Corneal confocal microscopy is a rapid, non-invasive ophthalmic technique to identify subclinical neuropathy. The aim of this study was to quantify Corneal Nerve morphology in children with type 1 diabetes mellitus compared with age-matched healthy controls using Corneal confocal microscopy. MATERIALS AND METHODS A total of 20 participants with type 1 diabetes mellitus (age 14 ± 2 years, diabetes duration 4.08 ± 2.91 years, glycated hemoglobin 9.3 ± 2.1%) without retinopathy or microalbuminuria and 20 healthy controls were recruited from outpatient clinics. Corneal confocal microscopy was undertaken, and Corneal Nerve fiber density (n/mm2 ), Corneal Nerve branch density (n/mm2 ), Corneal Nerve fiber length (mm/mm2 ), Corneal Nerve fiber tortuosity and inferior whorl length (mm/mm2 ) were quantified manually. RESULTS Corneal Nerve fiber density (22.73 ± 8.84 vs 32.92 ± 8.59; P < 0.001), Corneal Nerve branch density (26.19 ± 14.64 vs 47.34 ± 20.01; P < 0.001), Corneal Nerve fiber length (13.26 ± 4.06 vs 19.52 ± 4.54; P < 0.001) and inferior whorl length (15.50 ± 5.48 vs 23.42 ± 3.94; P < 0.0001) were significantly lower, whereas Corneal Nerve fiber tortuosity (14.88 ± 5.28 vs 13.52 ± 3.01; P = 0.323) did not differ between children with type 1 diabetes mellitus and controls. Glycated hemoglobin correlated with Corneal Nerve fiber tortuosity (P < 0.006) and aspartate aminotransferase correlated with Corneal Nerve fiber density (P = 0.039), Corneal Nerve branch density (P = 0.003) and Corneal Nerve fiber length (P = 0.037). CONCLUSION Corneal confocal microscopy identifies significant subclinical Corneal Nerve loss, especially in the inferior whorl of children with type 1 diabetes mellitus without retinopathy or microalbuminuria.

  • Corneal confocal microscopy identifies greater Corneal Nerve damage in patients with a recurrent compared to first ischemic stroke
    PLOS ONE, 2020
    Co-Authors: Adnan Khan, Georgios Ponirakis, Ioannis N. Petropoulos, Naveed Akhtar, Saadat Kamran, Hamad Almuhannadi, Blessy Babu, Namitha Jose, Rumissa Ibrahim, Hoda Gad
    Abstract:

    Objectives Corneal Nerve damage may be a surrogate marker for the risk of ischemic stroke. This study was undertaken to determine if there is greater Corneal Nerve damage in patients with recurrent ischemic stroke. Methods Corneal confocal microscopy (CCM) was used to quantify Corneal Nerve fiber density (CNFD), Corneal Nerve branch density (CNBD), Corneal Nerve fiber length (CNFL) and Corneal Nerve fiber tortuosity (CNFT) in 31 patients with recurrent ischemic stroke, 165 patients with a first acute ischemic stroke and 23 healthy control subjects. Results Triglycerides (P = 0.004, P = 0.017), systolic BP (P = 0.000, P = 0.000), diastolic BP (P = 0.000, P = 0.000) and HbA1c (P = 0.000, P = 0.000) were significantly higher in patients with first and recurrent stroke compared to controls. There was no difference in age, BMI, HbA1c, total cholesterol, triglycerides, LDL, HDL, systolic and diastolic BP between patients with a first and recurrent ischemic stroke. However, CNFD was significantly lower (24.98±7.31 vs 29.07±7.58 vs 37.91±7.13, P<0.05) and CNFT was significantly higher (0.085±0.042 vs 0.064±0.037 vs 0.039±0.022, P<0.05) in patients with recurrent stroke compared to first stroke and healthy controls. CNBD (42.21±24.65 vs 50.46±27.68 vs 87.24±45.85, P<0.001) and CNFL (15.66±5.70, P<0.001 vs 17.38±5.06, P = 0.003) were equally reduced in patients with first and recurrent stroke compared to controls (22.72±5.14). Conclusions Corneal confocal microscopy identified greater Corneal Nerve fibre loss in patients with recurrent stroke compared to patients with first stroke, despite comparable risk factors. Longitudinal studies are required to determine the prognostic utility of Corneal Nerve fiber loss in identifying patients at risk of recurrent ischemic stroke.

Georgios Ponirakis - One of the best experts on this subject based on the ideXlab platform.

  • Corneal confocal microscopy identifies Corneal Nerve fibre loss and increased dendritic cells in patients with long covid
    British Journal of Ophthalmology, 2021
    Co-Authors: Gulfidan Bitirgen, Georgios Ponirakis, Rayaz A Malik, Ahmet Ozkagnici, Celalettin Korkmaz, Adil Zamani, Nazmi Zengin
    Abstract:

    Background/Aims Long 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. Methods Forty 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. Results The 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). Conclusion Corneal 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.

  • insulin resistance limits Corneal Nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control
    Journal of Diabetes Investigation, 2021
    Co-Authors: Georgios Ponirakis, Ioannis N. Petropoulos, Hamad Almuhannadi, Muhammad A Abdulghani, Amin Jayyousi, Mahmoud Zirie, Salma Almohannadi, Adnan Khan
    Abstract:

    AIMS/INTRODUCTION This study aimed to investigate whether insulin resistance (IR) in individuals with type 2 diabetes undergoing intensive glycemic control determines the extent of improvement in neuropathy. MATERIALS AND METHODS This was an exploratory substudy of an open-label, randomized controlled trial of individuals with poorly controlled type 2 diabetes treated with exenatide and pioglitazone or insulin to achieve a glycated hemoglobin <7.0% (<53 mmol/mol). Baseline IR was defined using homeostasis model assessment of IR, and change in neuropathy was assessed using Corneal confocal microscopy. RESULTS A total of 38 individuals with type 2 diabetes aged 50.2 ± 8.5 years with (n = 25, 66%) and without (n = 13, 34%) IR were studied. There was a significant decrease in glycated hemoglobin (P < 0.0001), diastolic blood pressure (P < 0.0001), total cholesterol (P < 0.01) and low-density lipoprotein (P = 0.05), and an increase in bodyweight (P < 0.0001) with treatment. Individuals with homeostasis model assessment of IR <1.9 showed a significant increase in Corneal Nerve fiber density (P ≤ 0.01), length (P ≤ 0.01) and branch density (P ≤ 0.01), whereas individuals with homeostasis model assessment of IR ≥1.9 showed no change. IR was negatively associated with change in Corneal Nerve fiber density after adjusting for change in bodyweight (P < 0.05). CONCLUSIONS Nerve regeneration might be limited in individuals with type 2 diabetes and IR undergoing treatment with pioglitazone plus exenatide or insulin to improve glycemic control.

  • diagnosis of neuropathy and risk factors for Corneal Nerve loss in type 1 and type 2 diabetes a Corneal confocal microscopy study
    Diabetes Care, 2021
    Co-Authors: Maryam Ferdousi, Georgios Ponirakis, Ioannis N. Petropoulos, Omar Asghar, Uazman Alam, Alise Kalteniece, Shazli Azmi, Andrew Marshall, Catherine Fullwood
    Abstract:

    OBJECTIVE To assess the diagnostic utility of Corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for Corneal Nerve loss. RESEARCH DESIGN AND METHODS A total of 490 participants, including 72 healthy control subjects, 149 with type 1 diabetes, and 269 with type 2 diabetes, underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors. RESULTS Corneal Nerve fiber density (CNFD) (P CONCLUSIONS CCM identifies more severe Corneal Nerve loss in patients with type 1 compared with type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in Corneal Nerve fiber length differ between type 1 and type 2 diabetes.

  • Corneal confocal microscopy compared with quantitative sensory testing and Nerve conduction for diagnosing and stratifying the severity of diabetic peripheral neuropathy
    BMJ open diabetes research & care, 2020
    Co-Authors: Maryam Ferdousi, Georgios Ponirakis, Ioannis N. Petropoulos, Uazman Alam, Alise Kalteniece, Shazli Azmi, Anne Worthington, Luca Donofrio, Shaishav Dhage, Andrew Marshall
    Abstract:

    INTRODUCTION Diabetic neuropathy can be diagnosed and assessed using a number of techniques including Corneal confocal microscopy (CCM). RESEARCH DESIGN AND METHODS We 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). RESULTS Vibration 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%). CONCLUSION This 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.

  • Corneal Nerve loss in children with type 1 diabetes mellitus without retinopathy or microalbuminuria
    Journal of Diabetes Investigation, 2020
    Co-Authors: Hoda Gad, Georgios Ponirakis, Ioannis N. Petropoulos, Adnan Khan, Bara Aljarrah, Saras Saraswathi, Parul Singh, Souhaila Al Khodor, Mamoun Elawad, Wesam Almasri
    Abstract:

    AIMS/INTRODUCTION Corneal confocal microscopy is a rapid, non-invasive ophthalmic technique to identify subclinical neuropathy. The aim of this study was to quantify Corneal Nerve morphology in children with type 1 diabetes mellitus compared with age-matched healthy controls using Corneal confocal microscopy. MATERIALS AND METHODS A total of 20 participants with type 1 diabetes mellitus (age 14 ± 2 years, diabetes duration 4.08 ± 2.91 years, glycated hemoglobin 9.3 ± 2.1%) without retinopathy or microalbuminuria and 20 healthy controls were recruited from outpatient clinics. Corneal confocal microscopy was undertaken, and Corneal Nerve fiber density (n/mm2 ), Corneal Nerve branch density (n/mm2 ), Corneal Nerve fiber length (mm/mm2 ), Corneal Nerve fiber tortuosity and inferior whorl length (mm/mm2 ) were quantified manually. RESULTS Corneal Nerve fiber density (22.73 ± 8.84 vs 32.92 ± 8.59; P < 0.001), Corneal Nerve branch density (26.19 ± 14.64 vs 47.34 ± 20.01; P < 0.001), Corneal Nerve fiber length (13.26 ± 4.06 vs 19.52 ± 4.54; P < 0.001) and inferior whorl length (15.50 ± 5.48 vs 23.42 ± 3.94; P < 0.0001) were significantly lower, whereas Corneal Nerve fiber tortuosity (14.88 ± 5.28 vs 13.52 ± 3.01; P = 0.323) did not differ between children with type 1 diabetes mellitus and controls. Glycated hemoglobin correlated with Corneal Nerve fiber tortuosity (P < 0.006) and aspartate aminotransferase correlated with Corneal Nerve fiber density (P = 0.039), Corneal Nerve branch density (P = 0.003) and Corneal Nerve fiber length (P = 0.037). CONCLUSION Corneal confocal microscopy identifies significant subclinical Corneal Nerve loss, especially in the inferior whorl of children with type 1 diabetes mellitus without retinopathy or microalbuminuria.

Nathan Efron - One of the best experts on this subject based on the ideXlab platform.

  • no relation between the severity of Corneal Nerve epithelial and keratocyte cell morphology with measures of dry eye disease in type 1 diabetes
    Investigative Ophthalmology & Visual Science, 2018
    Co-Authors: Maryam Ferdousi, Georgios Ponirakis, Ioannis N. Petropoulos, Alise Kalteniece, Shazli Azmi, Handrean Soran, Rayaz A Malik, Nathan Efron
    Abstract:

    Purpose: Patients with diabetes have a propensity to develop dry eye symptoms (DES), with reduced tear secretion and Corneal sensitivity. The underlying pathologic basis of DES was explored in patients with Type 1 diabetes. Methods: Forty-two patients with Type 1 diabetes mellitus (T1DM) (age: 49.21 ± 2.53 years, duration of diabetes: 29.98 ± 2.64 years) and 25 control subjects (age: 48.70 ± 2.84 years) underwent assessment of DES using a validated dry eye questionnaire, and tear stability and tear production were assessed using tear breakup time (TBUT) and Schirmer's test, respectively. Corneal confocal microscopy was undertaken to quantify Corneal Nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), keratocyte density (KD), and Corneal epithelial basal cell (CEBC) density and area. Results: The prevalence of DES was significantly higher (P = 0.03), and TBUT (P = 0.006), Corneal sensation (P < 0.0001), CNFD (P = 0.001), CNBD (P = 0.001), CNFL (P = 0.003), and KD (P = 0.04) were significantly lower in patients with T1DM compared to control subjects. However, these measures did not differ significantly between T1DM patients with and without dry eye. There was no correlation between DES and TBUT or Corneal Nerve keratocyte and CEBC morphology. Conclusions: DES and TBUT are significantly increased in patients with T1DM, but are not related to Corneal Nerve, basal epithelial, or keratocyte cell morphology.

  • greater Corneal Nerve loss at the inferior whorl is related to the presence of diabetic neuropathy and painful diabetic neuropathy
    Scientific Reports, 2018
    Co-Authors: Alise Kalteniece, Hassan Fadavi, Ioannis N. Petropoulos, Maryam Ferdousi, Shazli Azmi, Andrew Marshall, Nathan Efron, Andrew J M Boulton, Safwaan Adam, Catharina G Faber
    Abstract:

    We assessed whether a measure of more distal Corneal Nerve fibre loss at the inferior whorl(IW) region is better than proximal measures of central Corneal Nerve damage in relation to the diagnosis of diabetic peripheral neuropathy(DPN), painful DPN and quality of life(QoL). Participants underwent detailed assessment of neuropathy, QoL using the SF36 questionnaire, pain visual analogue score(VAS), and Corneal confocal microscopy(CCM). Corneal Nerve fibre density (CNFD), branch density (CNBD) and length (CNFL) at the central cornea and inferior whorl length (IWL) and average(ANFL) and total(TNFL) Nerve fibre length were compared in patients with and without DPN and between patients with and without painful DPN and in relation to QoL. All CCM parameters were significantly reduced, but IWL was reduced ~three-fold greater than CNFL in patients with and without DPN compared to controls. IWL(p = 0.001), ANFL(p = 0.01) and TNFL(p = 0.02) were significantly lower in patients with painful compared to painless DPN. The VAS score correlated with IWL(r = −0.36, P = 0.004), ANFL(r = −0.32, P = 0.01) and TNFL(r = −0.32, P = 0.01) and QoL correlated with CNFL(r = 0.35, P = 0.01) and IWL(r = 0.4, P = 0.004). Corneal Nerve fibre damage is more prominent at the IW, lower in patients with painful compared to painless neuropathy and relates to their QoL. IWL may provide additional clinical utility for CCM in patients with DPN.

  • Corneal Nerve fractal dimension a novel Corneal Nerve metric for the diagnosis of diabetic sensorimotor polyneuropathy
    Investigative Ophthalmology & Visual Science, 2018
    Co-Authors: Xin Chen, Georgios Ponirakis, Ioannis N. Petropoulos, Omar Asghar, Uazman Alam, Maryam Ferdousi, Shazli Azmi, Andrew Marshall, Jim Graham, Nathan Efron
    Abstract:

    Objective: Corneal 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). Methods: A 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. Results: Manual 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. Conclusions: ACNFrD shows comparable diagnostic efficiency to identify diabetic patients with and without DSPN.

  • risk factors associated with Corneal Nerve alteration in type 1 diabetes in the absence of neuropathy a longitudinal in vivo Corneal confocal microscopy study
    Cornea, 2016
    Co-Authors: Cirous Dehghani, Nicola Pritchard, Katie Edwards, Rayaz A Malik, Anthony W Russell, Nathan Efron
    Abstract:

    The aim of this study was to determine alterations to the Corneal subbasal Nerve plexus (SNP) over 4 years using in vivo Corneal confocal microscopy in participants with type 1 diabetes and to identify significant risk factors associated with these alterations. A cohort of 108 individuals with type 1 diabetes and no evidence of peripheral neuropathy at enrollment underwent laser-scanning in vivo Corneal confocal microscopy, ocular screening, and health and metabolic assessment at baseline, and the examinations continued for 4 subsequent annual visits. At each annual visit, 8 central Corneal images of the SNP were selected and analyzed to quantify Corneal Nerve fiber density, Corneal Nerve branch density and Corneal Nerve fiber length. Linear mixed model approaches were fitted to examine the relationship between risk factors and Corneal Nerve parameters. A total of 96 participants completed the final visit and 91 participants completed all visits. No significant relationships were found between Corneal Nerve parameters and time, sex, duration of diabetes, smoking, alcohol consumption, blood pressure, or body mass index. However, Corneal Nerve fiber density was negatively associated with glycated hemoglobin (β = -0.76, P Glycemic control, high-density lipid, and age have significant effects on SNP structure. These findings highlight the importance of diabetic management to prevent Corneal Nerve damage and the capability of in vivo Corneal confocal microscopy for monitoring subclinical alterations in the Corneal SNP in diabetes.

  • risk factors associated with Corneal Nerve alteration in type 1 diabetes in the absence of neuropathy a longitudinal in vivo Corneal confocal microscopy study
    Faculty of Health; Institute of Health and Biomedical Innovation, 2016
    Co-Authors: Cirous Dehghani, Nicola Pritchard, Katie Edwards, Rayaz A Malik, Anthony W Russell, Nathan Efron
    Abstract:

    Purpose The aim of this study was to determine alterations to the Corneal subbasal Nerve plexus (SNP) over four years using in vivo Corneal confocal microscopy (IVCM) in participants with type 1 diabetes and to identify significant risk factors associated with these alterations. Methods A cohort of 108 individuals with type 1 diabetes and no evidence of peripheral neuropathy at enrollment underwent laser-scanning IVCM, ocular screening, and health and metabolic assessment at baseline and the examinations continued for four subsequent annual visits. At each annual visit, eight central Corneal images of the SNP were selected and analyzed to quantify Corneal Nerve fiber density (CNFD), branch density (CNBD) and fiber length (CNFL). Linear mixed model approaches were fitted to examine the relationship between risk factors and Corneal Nerve parameters. Results A total of 96 participants completed the final visit and 91 participants completed all visits. No significant relationships were found between Corneal Nerve parameters and time, sex, duration of diabetes, smoking, alcohol consumption, blood pressure or BMI. However, CNFD was negatively associated with HbA1c (β=-0.76, P<0.01) and age (β=-0.13, P<0.01) and positively related to high density lipids (HDL) (β=2.01, P=0.03). Higher HbA1c (β=-1.58, P=0.04) and age (β=-0.23, P<0.01) also negatively impacted CNBD. CNFL was only affected by higher age (β=-0.06, P<0.01). Conclusions Glycemic control, HDL and age have significant effects on SNP structure. These findings highlight the importance of diabetic management to prevent Corneal Nerve damage as well as the capability of IVCM for monitoring subclinical alterations in the Corneal SNP in diabetes.

Maryam Ferdousi - One of the best experts on this subject based on the ideXlab platform.

  • diagnosis of neuropathy and risk factors for Corneal Nerve loss in type 1 and type 2 diabetes a Corneal confocal microscopy study
    Diabetes Care, 2021
    Co-Authors: Maryam Ferdousi, Georgios Ponirakis, Ioannis N. Petropoulos, Omar Asghar, Uazman Alam, Alise Kalteniece, Shazli Azmi, Andrew Marshall, Catherine Fullwood
    Abstract:

    OBJECTIVE To assess the diagnostic utility of Corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for Corneal Nerve loss. RESEARCH DESIGN AND METHODS A total of 490 participants, including 72 healthy control subjects, 149 with type 1 diabetes, and 269 with type 2 diabetes, underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors. RESULTS Corneal Nerve fiber density (CNFD) (P CONCLUSIONS CCM identifies more severe Corneal Nerve loss in patients with type 1 compared with type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in Corneal Nerve fiber length differ between type 1 and type 2 diabetes.

  • Corneal confocal microscopy compared with quantitative sensory testing and Nerve conduction for diagnosing and stratifying the severity of diabetic peripheral neuropathy
    BMJ open diabetes research & care, 2020
    Co-Authors: Maryam Ferdousi, Georgios Ponirakis, Ioannis N. Petropoulos, Uazman Alam, Alise Kalteniece, Shazli Azmi, Anne Worthington, Luca Donofrio, Shaishav Dhage, Andrew Marshall
    Abstract:

    INTRODUCTION Diabetic neuropathy can be diagnosed and assessed using a number of techniques including Corneal confocal microscopy (CCM). RESEARCH DESIGN AND METHODS We 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). RESULTS Vibration 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%). CONCLUSION This 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.

  • Rapid Corneal Nerve Fiber Loss: A Marker of Diabetic Neuropathy Onset and Progression
    Diabetes Care, 2020
    Co-Authors: Evan J. H. Lewis, Leif E. Lovblom, Maryam Ferdousi, Elise M. Halpern, Maria Jeziorska, Danièle Pacaud, Nicola Pritchard, Cirous Dehghani, Katie Edwards, Sangeetha Srinivasan
    Abstract:

    OBJECTIVE Corneal Nerve fiber length (CNFL) represents a biomarker for diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the reference distribution of annual CNFL change, the prevalence of abnormal change in diabetes, and its associated clinical variables. RESEARCH DESIGN AND METHODS We examined 590 participants with diabetes [399 type 1 diabetes (T1D) and 191 type 2 diabetes (T2D)] and 204 control patients without diabetes with at least 1 year of follow-up and classified them according to rapid Corneal Nerve fiber loss (RCNFL) if CNFL change was below the fifth percentile of the control patients without diabetes. RESULTS Control patients without diabetes were 37.9 ± 19.8 years old, had median follow-up of three visits over 3.0 years, and mean annual change in CNFL was −0.1% (90% CI, −5.9 to 5.0%). RCNFL was defined by values exceeding the fifth percentile of 6% loss. Participants with T1D were 39.9 ± 18.7 years old, had median follow-up of three visits over 4.4 years, and mean annual change in CNFL was −0.8% (90% CI, −14.0 to 9.9%). Participants with T2D were 60.4 ± 8.2 years old, had median follow-up of three visits over 5.3 years, and mean annual change in CNFL was −0.2% (90% CI, −14.1 to 14.3%). RCNFL prevalence was 17% overall and was similar by diabetes type [64 T1D (16.0%), 37 T2D (19.4%), P = 0.31]. RNCFL was more common in those with baseline DSP (47% vs. 30% in those without baseline DSP, P = 0.001), which was associated with lower peroneal conduction velocity but not with baseline HbA1c or its change over follow-up. CONCLUSIONS An abnormally rapid loss of CNFL of 6% per year or more occurs in 17% of diabetes patients. RCNFL may identify patients at highest risk for the development and progression of DSP.

  • Diagnosis of Neuropathy and Risk Factors for Corneal Nerve Loss in Type 1 and Type 2 Diabetes: A Corneal Confocal Microscopy Study
    'American Diabetes Association', 2020
    Co-Authors: Maryam Ferdousi, Georgios Ponirakis, Alise Kalteniece, Shazli Azmi, Andrew Marshall, Catherine Fullwood, I.n. Petropoulos, U. Alam, O. Asghar, Maria Jeziorska
    Abstract:

    OBJECTIVE To assess the diagnostic utility of Corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for Corneal Nerve loss. RESEARCH DESIGN AND METHODS A total of 490 participants, including 72 healthy control subjects, 149 with type 1 diabetes, and 269 with type 2 diabetes, underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors. RESULTS Corneal Nerve fiber density (CNFD) (P < 0.0001 and P < 0.0001), Corneal Nerve fiber branch density (CNBD) (P < 0.0001 and P < 0.0001), and Corneal Nerve fiber length (CNFL) (P < 0.0001 and P = 0.02) were significantly lower in patients with type 1 and type 2 diabetes compared with control subjects. CNFD (P < 0.0001), CNBD (P < 0.0001), and CNFL (P < 0.0001) were lower in type 1 diabetes compared with type 2 diabetes. Receiver operating characteristic curve analysis for the diagnosis of DPN demonstrated a good area under the curve for CNFD of 0.81, CNBD of 0.74, and CNFL of 0.73. Multivariable regression analysis showed a significant association among reduced Corneal Nerve fiber length with age (\u3b2 = 120.27, P = 0.007), HbA1c (\u3b2 = 121.1; P = 0.01), and weight (\u3b2 = 120.14; P = 0.03) in patients with type 2 diabetes and with duration of diabetes (\u3b2 = 120.13; P = 0.02), LDL cholesterol (\u3b2 = 1.8, P = 0.04), and triglycerides (\u3b2 = 122.87; P = 0.009) in patients with type 1 diabetes. CONCLUSIONS CCM identifies more severe Corneal Nerve loss in patients with type 1 compared with type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in Corneal Nerve fiber length differ between type 1 and type 2 diabetes

  • early Corneal Nerve fibre damage and increased langerhans cell density in children with type 1 diabetes mellitus
    Scientific Reports, 2019
    Co-Authors: Maryam Ferdousi, Rayaz A Malik, Kenneth Romanchuk, Heidi Virtanen, Christine Millar, Danièle Pacaud
    Abstract:

    Corneal confocal microscopy (CCM) has been used to identify Corneal Nerve damage and increased Langerhans cell (LC) density in adults with Type 1 diabetes mellitus (T1DM). The purpose of this study was to evaluate whether Corneal confocal microscopy can identify early Corneal Nerve damage and change in LC density in children and adolescents with T1DM. 64 participants with T1DM (age-14.6 ± 2.5 years, duration of diabetes-9.1 ± 2.7 years, HbA1c-75.66 ± 2.53 mmol/mol [9.1 ± 1.8%]) and 48 age-matched healthy control subjects underwent CCM. Sub-basal Corneal Nerve morphology and the density of mature and immature LCs was quantified. Corneal Nerve fibre length and branch density were lower, whilst fibre density and tortuosity did not differ and both immature and mature LC density was significantly higher in T1DM compared to control subjects. There was no association between HbA1c and duration of diabetes with Nerve fibre parameters or LC’s density. Children and adolescents with T1DM demonstrate early immune activation and Nerve degeneration.