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Corneal Confocal Microscopy detects a Reduction in Corneal Endothelial Cells and Nerve Fibres in Patients with Acute Ischemic Stroke.

ABSTRACT: Endothelial dysfunction and damage underlie cerebrovascular disease and ischemic stroke. We undertook corneal confocal microscopy (CCM) to quantify corneal endothelial cell and nerve morphology in 146 patients with an acute ischemic stroke and 18 age-matched healthy control participants. Corneal endothelial cell density was lower (P?

SUBMITTER: Khan A

PROVIDER: S-EPMC6255787 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Corneal Confocal Microscopy detects a Reduction in Corneal Endothelial Cells and Nerve Fibres in Patients with Acute Ischemic Stroke.

Khan Adnan A Kamran Saadat S Akhtar Naveed N Ponirakis Georgios G Al-Muhannadi Hamad H Petropoulos Ioannis N IN Al-Fahdawi Shumoos S Qahwaji Rami R Sartaj Faheem F Babu Blessy B Wadiwala Muhammad Faisal MF Shuaib Ashfaq A Malik Rayaz A RA

Scientific reports 20181126 1

Endothelial dysfunction and damage underlie cerebrovascular disease and ischemic stroke. We undertook corneal confocal microscopy (CCM) to quantify corneal endothelial cell and nerve morphology in 146 patients with an acute ischemic stroke and 18 age-matched healthy control participants. Corneal endothelial cell density was lower (P < 0.001) and endothelial cell area (P < 0.001) and perimeter (P < 0.001) were higher, whilst corneal nerve fibre density (P < 0.001), corneal nerve branch density (P ...[more]

PMID: 30478334

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Corneal confocal microscopy identifies greater corneal nerve damage in patients with a recurrent compared to first ischemic stroke.

Project description: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.

| S-EPMC7176137 | biostudies-literature

Corneal confocal microscopy detects corneal nerve damage and increased dendritic cells in Fabry disease.

Project description: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 (??=?-0.686; P?=?0.006), NFL (??=?-0.692; P?=?0.006), endothelial cell density (??=?-0.511; P?=?0.036), endothelial cell area (??=?0.514; P?=?0.036) and ?-galactosidase A enzyme activity (??=?-0.723; P?=?0.008). This study demonstrates reduced corneal sensitivity, corneal nerve fiber damage and increased DCs in subjects with Fabry disease.

| S-EPMC6095897 | biostudies-other

Corneal confocal microscopy detects small nerve fibre damage in patients with painful diabetic neuropathy.

Project description:Neuropathic pain is believed to arise from damage to nociceptive C fibres in diabetic neuropathy (DN). We have utilised corneal confocal microscopy (CCM) to quantify the severity of small nerve fibre damage in relation to the severity of neuropathic pain and quality of life (QoL) in patients with and without painful DN. 30 controls and patients with painful (n?=?78) and painless (n?=?62) DN underwent assessment of large and small nerve fibre function, CCM, neuropathic symptoms (small fibre neuropathy symptom inventory questionnaire, neuropathic pain scale) and QoL (SF-36, pre-R-ODS and hospital anxiety and depression scale). Patients with painful compared to painless DN, had comparable neurophysiology and vibration perception, but lower corneal nerve fibre density (20.1?±?0.87 vs. 24.13?±?0.91, P?=?0.005), branch density (44.4?±?3.31 vs. 57.74?±?3.98, P?=?0.03), length (19.61?±?0.81 vs. 22.77?±?0.83, P?=?0.01), inferior whorl length (18.03?±?1.46 vs. 25.1?±?1.95, P?=?0.005) and cold sensation threshold (21.35?±?0.99 vs. 26.08?±?0.5, P?<?0.0001) and higher warm sensation threshold (43.7?±?0.49 vs. 41.37?±?0.51, P?=?0.004) indicative of small fibre damage. There was a significant association between all CCM parameters and the severity of painful neuropathic symptoms, depression score and QoL. CCM identifies small nerve fibre loss, which correlates with the severity of neuropathic symptoms and reduced QoL in patients with painful diabetic neuropathy.

| S-EPMC7042367 | biostudies-literature

Analysis of corneal nerve plexus in corneal confocal microscopy images.

Project description: Not available

| S-EPMC8067927 | biostudies-literature

Corneal Confocal Microscopy Demonstrates Corneal Nerve Loss in Patients With Trigeminal Neuralgia.

Project description: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.

| S-EPMC7393442 | biostudies-literature

Corneal nerve and endothelial cell damage in patients with transient ischemic attack and minor ischemic stroke.

Project description:ObjectiveTo determine if corneal confocal microscopy can identify corneal nerve and endothelial cell abnormalities and may be useful in the prognostication of patients with transient ischemic attack [1] or minor ischemic stroke (IS).MethodsThirty-six patients admitted with TIA (n = 14) or minor IS (n = 22) underwent transcranial Doppler evaluation and corneal confocal microscopy and were compared with 18 healthy controls.ResultsCorneal nerve fiber density (P = 0.002), branch density (P = 0.004) and fiber length (P = 0.004) were significantly lower in patients with TIA or minor IS compared to controls, with no difference between patients with TIA and minor IS. Endothelial cell density (P = 0.003) was lower and endothelial cell area (P = 0.003) and perimeter (P = 0.006) were significantly higher in patients with TIA or minor IS compared to controls, with no difference between patients with TIA and minor IS. There were no differences in corneal nerve or endothelial cell morphology between patients with and without abnormal cerebrovascular reactivity. HbA1c was independently associated with CNFL, and endothelial cell polymegathism and pleomorphism were associated with both HbA1c and total cholesterol.ConclusionCorneal confocal microscopy identifies corneal nerve fiber loss and endothelial cell abnormalities in patients with TIA and minor IS and independent associations with HbA1c and cholesterol.

| S-EPMC6420175 | biostudies-literature

Corneal confocal microscopy is a rapid reproducible ophthalmic technique for quantifying corneal nerve abnormalities.

Project description:PurposeTo assess the effect of applying a protocol for image selection and the number of images required for adequate quantification of corneal nerve pathology using in vivo corneal confocal microscopy (IVCCM).MethodsIVCCM was performed in 35 participants by a single examiner. For each participant, 4 observers used a standardized protocol to select 6 central corneal nerve images to assess the inter-observer variability. Furthermore, images were selected by a single observer on two occasions to assess intra-observer variability and the effect of sample size was assessed by comparing 6 with 12 images. Corneal nerve fiber density (CNFD), branch density (CNBD) and length (CNFL) were quantified using fully automated software. The data were compared using the intra class correlation coefficient (ICC) and Bland-Altman agreement plots for all experiments.ResultsThe ICC values for CNFD, CNBD and CNFL were 0.93 (P<0.0001), 0.96 (P<0.0001) and 0.95 (P<0.0001) for inter-observer variability and 0.95 (P<0.0001), 0.97 (P<0.001) and 0.97 (P<0.0001) for intra-observer variability. For sample size variability, ICC values were 0.94 (P<0.0001), 0.95 (P<0.0001), and 0.96 (P<0.0001) for CNFD, CNBD and CNFL. Bland-Altman plots showed excellent agreement for all parameters.ConclusionsThis study shows that implementing a standardized protocol to select IVCCM images results in high intra and inter-observer reproducibility for all corneal nerve parameters and 6 images are adequate for analysis. IVCCM could therefore be deployed in large multicenter clinical trials with confidence.

| S-EPMC5560560 | biostudies-literature

Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy.

Project description:There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04) and warm sensation (P = 0.03) thresholds with a significantly reduced sural sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length (CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the severity of lymph node involvement. After the 3rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.

| S-EPMC4592260 | biostudies-literature

In Vivo Confocal Microscopy Shows Alterations in Nerve Density and Dendritiform Cell Density in Fuchs' Endothelial Corneal Dystrophy.

Project description:PurposeTo evaluate corneal nerve and immune cell alterations in Fuchs' endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) by laser in vivo confocal microscopy (IVCM) as correlated to corneal sensation and endothelial cell loss.DesignProspective, cross-sectional, controlled study.MethodsThirty-three eyes with FECD were compared to 13 eyes with PBK and 17 normal age-matched control eyes at a tertiary referral center. FECD was classified into early (without edema) and late stage (with edema). Corneal IVCM and esthesiometry were performed. Corneal nerve and immune dendritiform cell (DC) alterations were evaluated and correlated to clinical parameters.ResultsFECD and PBK eyes showed significantly (P = .001) diminished total nerve length (11.5 ± 1.3 and 2.9 ± 0.7 mm/mm2) and number (8.8 ± 1.1 and 2.2 ± 0.4 n/frame), compared to controls (23.3 ± 8.1 mm/mm2 and 25.9 ± 1.3 n/frame). Decreased nerves corresponded to diminished sensation in FECD (4.9 ± 0.2 cm; R = 0.32; P = .045), compared to controls (5.9 ± 0.04 cm). Early- and late-stage FECD showed significantly reduced total nerve length (13.1 ± 1.4 and 9.9 ± 1.2 mm/mm2, respectively) and number (8.2 ± 2.5 and 6.5 ± 2.1 n/frame), compared to controls (P < .001). DC density was significantly increased in FECD (57.8 ± 10.4 cells/mm2; P = .01), but not in PBK (47.7 ± 11.6 cells/mm2; P = .60) compared to controls (22.5 ± 4.5 cells/mm2). A subset of early FECD patients (7/22) demonstrated very high DC density (>100/mm2).ConclusionIVCM demonstrates profound diminishment of subbasal corneal nerves in early- and late-stage FECD and in PBK, correlating to decreased sensation. Increased DC density in early FECD demonstrates potential subclinical inflammation. The data suggest that reduction in subbasal nerves and increased immune activation may play a role in the pathophysiology of FECD.

| S-EPMC6420962 | biostudies-literature

Longitudinal study on nerve ultrasound and corneal confocal microscopy in NF155 paranodopathy.

Project description:We report the case of a 27-year-old patient with subacute anti-neurofascin-155 neuropathy with bifacial palsy, who showed excellent response to rituximab. We provide longitudinal data of established clinical scores, nerve conduction studies, antibody titers, and novel imaging methods (nerve ultrasonography and corneal confocal microscopy). Clinical and electrophysiological improvement followed the reduction of serum antibody titer and correlated with a reduction of corneal inflammatory cellular infiltrates whereas the increase in the cross-sectional area of the peripheral nerves remained 12 months after first manifestation. Our findings suggest that novel techniques provide useful follow-up parameters in paranodopathies.

| S-EPMC7318093 | biostudies-literature

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