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

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).

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

Scientific Reports ◽

10.1038/s41598-021-01226-1 ◽

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.

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

10.1101/2020.04.19.048926 ◽

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.

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The Use of Corneal Confocal Microscopy for Early Detection of the Affection of Corneal Nerve Fibers in Patients with Type 2 Diabetes

Acta Endocrinologica (Bucharest) ◽

10.4183/aeb.2015.55 ◽

2015 ◽

Vol 11 (1) ◽

pp. 55-59

Author(s):

M Burcea

Keyword(s):

Type 2 Diabetes ◽

Confocal Microscopy ◽

Early Detection ◽

Nerve Fibers ◽

Corneal Confocal Microscopy ◽

Corneal Nerve

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

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217321998060 ◽

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.

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

Stroke ◽

10.1161/strokeaha.117.018289 ◽

2017 ◽

Vol 48 (11) ◽

pp. 3012-3018 ◽

Cited By ~ 11

Author(s):

Adnan Khan ◽

Naveed Akhtar ◽

Saadat Kamran ◽

Georgios Ponirakis ◽

Ioannis N. Petropoulos ◽

...

Keyword(s):

Ischemic Stroke ◽

Confocal Microscopy ◽

Acute Ischemic Stroke ◽

Nerve Damage ◽

Corneal Confocal Microscopy ◽

Corneal Nerve

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Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-319450 ◽

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.

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