scholarly journals A novel investigation method for axonal damage in neuromyelitis optica spectrum disorder: In vivo corneal confocal microscopy

2021 ◽  
Vol 7 (1) ◽  
pp. 205521732199806
Author(s):  
Ayşe Altıntaş ◽  
Ayse Yildiz-Tas ◽  
Sezen Yilmaz ◽  
Betul N Bayraktutar ◽  
Melis Cansu Comert ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Nerve Fibre ◽  
Disease Severity ◽  
Neuromyelitis Optica ◽  
Spectrum Disorder ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Rnfl Thickness ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

Background Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disorder that damages optic nerves, brainstem, and spinal cord. In vivo corneal confocal microscopy (IVCM) is a noninvasive technique that provides corneal images with dendritic cells (DCs) and corneal subbasal nerve plexus (SBP), which arises from the trigeminal nerve. Objective We investigated corneal SBP changes in NMOSD and proposed IVCM as a potential new disease severity biomarker for NMOSD. Methods Seventeen age-sex matched NMOSD patients and 19 healthy participants underwent complete neurologic and ophthalmologic examinations. The duration of disease, first symptom, presence of optic neuritis attack, antibody status, Expanded Disability Status Scale(EDSS) score and disease severity score(DSS) were recorded. Retinal nerve fibre layer (RNFL) thickness was measured with optical coherence tomography, and corneal SBP images were taken with IVCM. Results NMOSD patients had significantly reduced corneal nerve fibre lenght-density and corneal nerve branch lenght-density compared with controls, while DC density was increased. NMOSD patients also showed significantly reduced RNFL thickness compared with controls. EDSS,DSS levels were inversely correlated with IVCM parameters. Conclusion We observed significant corneal nerve fibre loss in NMOSD patients in relation to disease severity. IVCM can be a candidate noninvasive imaging method for axonal damage assessment in NMOSD that warrants further investigation.

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

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

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

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 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 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 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 In vivo corneal confocal microscopy and optical coherence tomography on eyes of participants with type 2 diabetes mellitus and obese participants without diabetes

2021 ◽  
Author(s):  
Noémi Tóth ◽  
David M. Silver ◽  
Szabolcs Balla ◽  
Miklós Káplár ◽  
Adrienne Csutak
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Optical Coherence Tomography ◽  
Type 2 Diabetes Mellitus ◽  
Confocal Microscopy ◽  
Nerve Fibers ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

Abstract Purposes To examine corneal nerve and retinal nerve characteristics of participants with type 2 diabetes mellitus (T2DM) compared with obese participants without diabetes to discover potential nerve vulnerabilities. Methods All participants underwent a complete medical examination including a physical examination and blood sample tests. The ophthalmologic examination included best-corrected visual acuity, intraocular pressure, Schirmer test, tear film breakup time, slit-lamp examination, dilated fundus photography, in vivo corneal confocal microscopy (IVCCM), and optical coherence tomography (OCT). Results The study cohort consisted of 83 eyes of 83 individuals: a group of 44 participants with T2DM, and a control group of 39 obese participants with no history of diabetes. Comparing measurements on the two groups, participants with T2DM had lower values with statistical significance for retinal nerve fiber layer (RNFL) nasal superior thickness (p = 0.010) and three corneal nerve (CN) parameters: fiber length (p = 0.025), total branch density (p = 0.013), and fiber area (p = 0.009). There was a borderline significant difference in CN fiber width (p = 0.051) and RNFL nasal inferior thickness (p = 0.056). No other significant differences were observed in the IVCCM and OCT parameters. No statistically significant correlation was found between CN and RNFL parameters. Conclusions Progression from a pre-diabetic obese state to a T2DM condition might entail a loss or diminishment of certain corneal nerve fibers or retinal nerve fibers, but not necessarily a loss of both corneal and retinal nerve fibers simultaneously. Using IVCCM and OCT together enables monitoring of both corneal and retinal health of the eye.

scholarly journals Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Patrick Schindler ◽  
Ulrike Grittner ◽  
Johanna Oechtering ◽  
David Leppert ◽  
Nadja Siebert ◽  
...  
Keyword(s):  
Disease Severity ◽  
Neuromyelitis Optica ◽  
Single Molecule ◽  
Effect Size ◽  
Clinical Remission ◽  
Spectrum Disorder ◽  
Aquaporin 4 ◽  
Prognostic Biomarkers ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Neurofilament Light

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is a frequently disabling neuroinflammatory syndrome with a relapsing course. Blood-based disease severity and prognostic biomarkers for NMOSD are a yet unmet clinical need. Here, we evaluated serum glial fibrillary acidic protein (sGFAP) and neurofilament light (sNfL) as disease severity and prognostic biomarkers in patients with aquaporin-4 immunoglobulin (Ig)G positive (AQP4-IgG+) NMOSD. Methods sGFAP and sNfL were determined by single-molecule array technology in a prospective cohort of 33 AQP4-IgG+ patients with NMOSD, 32 of which were in clinical remission at study baseline. Sixteen myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG+) patients and 38 healthy persons were included as controls. Attacks were recorded in all AQP4-IgG+ patients over a median observation period of 4.25 years. Results In patients with AQP4-IgG+ NMOSD, median sGFAP (109.2 pg/ml) was non-significantly higher than in MOG-IgG+ patients (81.1 pg/ml; p = 0.83) and healthy controls (67.7 pg/ml; p = 0.07); sNfL did not substantially differ between groups. Yet, in AQP4-IgG+, but not MOG-IgG+ patients, higher sGFAP was associated with worse clinical disability scores, including the Expanded Disability Status Scale (EDSS, standardized effect size = 1.30, p = 0.007) and Multiple Sclerosis Functional Composite (MSFC, standardized effect size = − 1.28, p = 0.01). While in AQP4-IgG+, but not MOG-IgG+ patients, baseline sGFAP and sNfL were positively associated (standardized effect size = 2.24, p = 0.001), higher sNfL was only non-significantly associated with worse EDSS (standardized effect size = 1.09, p = 0.15) and MSFC (standardized effect size = − 1.75, p = 0.06) in patients with AQP4-IgG+ NMOSD. Patients with AQP4-IgG+ NMOSD with sGFAP > 90 pg/ml at baseline had a shorter time to a future attack than those with sGFAP ≤ 90 pg/ml (adjusted hazard ratio [95% confidence interval] = 11.6 [1.3–105.6], p = 0.03). In contrast, baseline sNfL levels above the 75th age adjusted percentile were not associated with a shorter time to a future attack in patients with AQP4-IgG+ NMOSD. Conclusion These findings suggest a potential role for sGFAP as biomarker for disease severity and future disease activity in patients with AQP4-IgG+ NMOSD in phases of clinical remission.

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.

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