scholarly journals T13. CORNEAL CONFOCAL MICROSCOPY DETECTS NEURAL CHANGES IN SCHIZOPHRENIA

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S235-S236
Author(s):  
Peter Woodruff ◽  
Georgios Ponirakis ◽  
Reem Ghandi ◽  
Amani Hussein ◽  
Anjushri Bhagat ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Confocal Microscopy ◽  
Negative Symptoms ◽  
High Density Lipoproteins ◽  
Healthy Controls ◽  
Sudomotor Function ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve ◽  
Function Testing ◽  
Positive And Negative Symptoms

Abstract Background A combination of neurodevelopmental and degenerative neural changes are likely to underpin positive and negative symptoms in schizophrenia. However, there are currently no validated biomarkers to accurately quantify the extent of neural changes in schizophrenia. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique that has been used to demonstrate in vivo corneal nerve fiber abnormalities in a range of peripheral neuropathies and central neurodegenerative disorders including Parkinson’s disease, multiple sclerosis and dementia. We wished to test the hypothesis that corneal nerve abnormalities occur in patients with schizophrenia, particularly those with negative symptoms and cognitive impairment. Methods Patients with DSM-V schizophrenia without other causes of peripheral neuropathy other than metabolic syndrome underwent assessment of clinical ratings (Positive and Negative Symptoms Scale (PANSS), cognitive function (Montreal Cognitive Assessment (MOCA) and Corneal confocal microscopy (CCM), vibration perception threshold (VPT) and sudomotor function testing. Healthy controls underwent the same assessments apart from PANSS. Results 55 subjects without (n=38) and with schizophrenia (n=17) with comparable mean age (35.7±8.5 vs 35.6±12.2, P=0.96) were studied. Patients with schizophrenia had significantly higher body weight (93.9±25.5 vs 77.1±10.1, P=0.02) and lower Low Density Lipoproteins (2.6±1.0 vs 3.4±0.7, P=0.02) compared with healthy controls. The proportion of gender, systolic and diastolic blood pressure, HbA1c, cholesterol, triglyceride and High Density Lipoproteins were comparable between the two groups. Patients with schizophrenia had significantly lower corneal nerve fibre density (CNFD, fibers/mm2) (35.6±6.5 vs 23.5±7.8, p<0.0001), branch density (CNBD, branches/mm2) (98.1±30.6 vs 34.4±26.9, p<0.0001), and fibre length (CNFL, mm/mm2) (24.2±3.9 vs 14.3±4.7, p<0.0001) compared with healthy controls but no difference in peripheral neuropathy assessed by VPT and sudomotor function testing. The area under the Receiver Operating Characteristic Curve (95% CI) of CNFD, CNBD, CNFL to distinguish patients with schizophrenia from healthy controls were 87.0% (76.8–98.2%), 93.2% (84.2–102.3%), 93.2% (84.4–102.1%), respectively. Discussion These preliminary results:

scholarly journals Using corneal confocal microscopy to compare Mecobalamin intramuscular injections vs oral tablets in treating diabetic peripheral neuropathy: a RCT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuanjin Zhang ◽  
Dongsheng Fan ◽  
Yixuan Zhang ◽  
Shuo Zhang ◽  
Haikun Wang ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Confocal Microscopy ◽  
Nerve Fibre ◽  
Diabetic Peripheral Neuropathy ◽  
Controlled Study ◽  
Oral Tablet ◽  
Injection Treatment ◽  
Intramuscular Injections ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

AbstractThis randomized controlled study used corneal confocal microscopy (CCM) to compare the efficacy of Mecobalamin intramuscular injections vs oral tablets in treating mild to moderate diabetic peripheral neuropathy (DPN) by detecting early nerve fiber repair. Enrolled patients were randomized approximately 1:1 to receive Mecobalamin intramuscular injections (0.5 mg/day, 3 times/week) or Mecobalamin oral tablets (1.5 mg/day) for 8 weeks. Primary outcome was change of inferior whorl length (IWL) from baseline. Secondary outcomes included changes of corneal nerve fibre length (CNFL), corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and the Survey of Autonomic Symptoms (SAS). 15 (93.75%) patients in the injection group and 17 (89.47%) patients in the tablet group completed the study. The injection treatment significantly improved patients’ IWL from baseline (21.64 ± 3.00 mm/mm2 vs 17.64 ± 4.83 mm/mm2, P < 0.01) while the tablet treatment didn’t. Additionally, the injection treatment led to significantly improved CNFL, CNBD and SAS from baseline (all P < 0.05) while the tablet treatment did not. No patient experienced any adverse events. In conclusion, CCM is sensitive enough to detect the superior efficacy of 8-week Mecobalamin intramuscular injection treatment for DPN compared to the oral tablet treatment.ClinicalTrials.gov registration number: NCT04372316 (30/04/2020).

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

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

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

scholarly journals Corneal dendritic cells and the subbasal nerve plexus following neurotoxic treatment with oxaliplatin or paclitaxel

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeremy Chung Bo Chiang ◽  
David Goldstein ◽  
Azadeh Tavakoli ◽  
Terry Trinh ◽  
Jacob Klisser ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Confocal Microscopy ◽  
Immune Cell ◽  
Healthy Controls ◽  
Corneal Confocal Microscopy ◽  
Significant Difference ◽  
Corneal Nerve ◽  
Cell Densities

AbstractImmune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm2) compared to healthy controls (Md = 10.1 cells/mm2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p < 0.05). There is evidence of elevation of corneal ImDC in oxaliplatin-treated patients. Further investigation is required to explore this potential link through longitudinal studies and animal or laboratory-based immunohistochemical research.

Corneal confocal microscopy identifies a reduction in corneal keratocyte density and sub-basal nerves in children with type 1 diabetes mellitus

2021 ◽  
pp. bjophthalmol-2021-319057
Author(s):  
Hoda Gad ◽  
Bara Al-Jarrah ◽  
Saras Saraswathi ◽  
Sara Mohamed ◽  
Alise Kalteniece ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Confocal Microscopy ◽  
Type 1 Diabetes Mellitus ◽  
Nerve Fibre ◽  
Healthy Controls ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve ◽  
Keratocyte Density

PurposeTo assess whether alterations in stromal keratocyte density are related to loss of corneal nerve fibres in children with type 1 diabetes mellitus (T1DM).MethodsTwenty participants with T1DM and 20 age-matched healthy controls underwent corneal confocal microscopy. Corneal sub-basal nerve morphology and corneal keratocyte density (KD) were quantified.ResultsCorneal nerve fibre density (CNFD) (p<0.001), corneal nerve branch density (p<0.001), corneal nerve fibre length (CNFL) (p<0.001) and inferior whorl length (IWL) (p<0.001) were lower in children with T1DM compared with healthy controls. Anterior (p<0.03) and mid (p=0.03) stromal KDs were lower with no difference in posterior KD (PKD) in children with T1DM compared with controls. Age, duration of diabetes, height, weight and body mass index did not correlate with anterior (AKD), mid (MKD) or PKD. Inverse correlations were found between glycated haemoglobin and PKD (r=−0.539, p=0.026), bilirubin with MKD (r=−0.540, p=0.025) and PKD (r=−0.531, p=0.028) and 25-hydroxycholecalciferol with MKD (r=−0.583, p=0.018). CNFD, CNFL and IWL did not correlate with AKD, MKD or PKD.ConclusionThis study demonstrates a reduction in corneal nerves and anterior and mid stromal KD in children with T1DM, but no correlation between corneal nerve and keratocyte cell loss.

scholarly journals Corneal Nerve Loss Detected With Corneal Confocal Microscopy Is Symmetrical and Related to the Severity of Diabetic Polyneuropathy

Diabetes Care ◽  
2013 ◽  
Vol 36 (11) ◽  
pp. 3646-3651 ◽  
Author(s):  
I. N. Petropoulos ◽  
U. Alam ◽  
H. Fadavi ◽  
O. Asghar ◽  
P. Green ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Diabetic Polyneuropathy ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

scholarly journals Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ioannis N. Petropoulos ◽  
Kathryn C. Fitzgerald ◽  
Jonathan Oakley ◽  
Georgios Ponirakis ◽  
Adnan Khan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Confocal Microscopy ◽  
Nerve Fiber ◽  
Clinically Isolated Syndrome ◽  
Axonal Loss ◽  
Fiber Density ◽  
Corneal Confocal Microscopy ◽  
Segmentation Methods ◽  
Relapsing Remitting ◽  
Corneal Nerve

AbstractAxonal loss is the main determinant of disease progression in multiple sclerosis (MS). This study aimed to assess the utility of corneal confocal microscopy (CCM) in detecting corneal axonal loss in different courses of MS. The results were confirmed by two independent segmentation methods. 72 subjects (144 eyes) [(clinically isolated syndrome (n = 9); relapsing–remitting MS (n = 20); secondary-progressive MS (n = 22); and age-matched, healthy controls (n = 21)] underwent CCM and assessment of their disability status. Two independent algorithms (ACCMetrics; and Voxeleron deepNerve) were used to quantify corneal nerve fiber density (CNFD) (ACCMetrics only), corneal nerve fiber length (CNFL) and corneal nerve fractal dimension (CNFrD). Data are expressed as mean ± standard deviation with 95% confidence interval (CI). Compared to controls, patients with MS had significantly lower CNFD (34.76 ± 5.57 vs. 19.85 ± 6.75 fibers/mm2, 95% CI − 18.24 to − 11.59, P < .0001), CNFL [for ACCMetrics: 19.75 ± 2.39 vs. 12.40 ± 3.30 mm/mm2, 95% CI − 8.94 to − 5.77, P < .0001; for deepNerve: 21.98 ± 2.76 vs. 14.40 ± 4.17 mm/mm2, 95% CI − 9.55 to − 5.6, P < .0001] and CNFrD [for ACCMetrics: 1.52 ± 0.02 vs. 1.45 ± 0.04, 95% CI − 0.09 to − 0.05, P < .0001; for deepNerve: 1.29 ± 0.03 vs. 1.19 ± 0.07, 95% − 0.13 to − 0.07, P < .0001]. Corneal nerve parameters were comparably reduced in different courses of MS. There was excellent reproducibility between the algorithms. Significant corneal axonal loss is detected in different courses of MS including patients with clinically isolated syndrome.

scholarly journals Combining In Vivo Corneal Confocal Microscopy with Deep Learning-based Analysis Reveals Sensory Nerve Fiber Loss in Acute SIV Infection

2020 ◽  
Author(s):  
Megan E. McCarron ◽  
Rachel L. Weinberg ◽  
Jessica M. Izzi ◽  
Suzanne E. Queen ◽  
Stuti L. Misra ◽  
...  
Keyword(s):  
Fractal Dimension ◽  
Deep Learning ◽  
Confocal Microscopy ◽  
Nerve Fiber ◽  
Fiber Length ◽  
Sensory Nerve ◽  
Corneal Confocal Microscopy ◽  
Siv Infection ◽  
Corneal Nerve

AbstractPurposeTo characterize corneal subbasal nerve plexus morphologic features using in vivo corneal confocal microscopy (IVCM) in normal and SIV-infected macaques and to implement automated assessments using novel deep learning-based methods customized for macaque studies.MethodsIn vivo corneal confocal microscopy images were collected from both male and female age-matched specific-pathogen free rhesus and pigtailed macaques housed at the Johns Hopkins University breeding colony using the Heidelberg HRTIII with Rostock Corneal Module. We also obtained repeat IVCM images of 12 SIV-infected animals including pre-infection and 10 day post-SIV infection time-points. All IVCM images were analyzed using a novel deep convolutional neural network architecture developed specifically for macaque studies.ResultsDeep learning-based segmentation of subbasal nerves in IVCM images from macaques demonstrated that corneal nerve fiber length (CNFL) and fractal dimension measurements did not differ between species, but pigtailed macaques had significantly higher baseline corneal nerve fiber tortuosity than rhesus macaques (P = 0.005). Neither sex nor age of macaques was associated with differences in any of the assessed corneal subbasal nerve parameters. In the SIV/macaque model of HIV, acute SIV infection induced significant decreases in both corneal nerve fiber length and fractal dimension (P= 0.01 and P= 0.008 respectively).ConclusionsThe combination of IVCM and objective, robust, and rapid deep-learning analysis serves as a powerful noninvasive research and clinical tool to track sensory nerve damage, enabling early detection of neuropathy. Adapting the deep-learning analyses to human corneal nerve assessments will refine our ability to predict and monitor damage to small sensory nerve fibers in a number of clinical settings including HIV, multiple sclerosis, Parkinson’s disease, diabetes, and chemotherapeutic neurotoxicity.

scholarly journals Artificial Intelligence–Based Classification of Diabetic Peripheral Neuropathy From Corneal Confocal Microscopy Images

Diabetes Care ◽  
2021 ◽  
pp. dc202012
Author(s):  
Tooba Salahouddin ◽  
Ioannis N. Petropoulos ◽  
Maryam Ferdousi ◽  
Georgios Ponirakis ◽  
Omar Asghar ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Peripheral Neuropathy ◽  
Confocal Microscopy ◽  
Diabetic Peripheral Neuropathy ◽  
Corneal Confocal Microscopy ◽  
Microscopy Images
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