Corneal confocal microscopy shows progressive reduction in corneal nerve fiber length over a 2 year time period in children with type 1 diabetes

Purpose. The purpose of our study is to describe the in vivo corneal confocal microscopy characteristics of subbasal nerve plexus in a highly selected population of patients affected by type 1 diabetes mellitus (T1DM) without any microvascular diabetes complications.Methods. We included 19 T1DM patients without diabetic peripheral neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, and microalbuminuria. All patients underwent in vivo corneal confocal microscopy and blood analysis to determine subbasal nerve plexus parameters and their correlation with clinical data. We compared the results with 19 healthy controls.Results. The T1DM group showed a significant decrease of the nerve fiber length (P=0.032), the nerve fiber length density (P=0.034), the number of fibers (P=0.005), and the number of branchings (P=0.028), compared to healthy subjects. The nerve fiber length, nerve fiber length density, and number of fibers were directly related to the age at onset of diabetes and inversely to the duration of DM. BMI (body mass index) was highly related to the nerve fiber length (r = −0.6,P=0.007), to the nerve fiber length density (r = −0.6,P=0.007), and to the number of fibers (r = −0.587,P=0.008). No significant correlations were found between the corneal parameters and HbA1c.Conclusions. Early subclinical fiber corneal variation could be easily detected using in vivo corneal confocal microscopy, even in type 1 diabetes without any microvascular diabetes complications, including diabetic peripheral neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, and microalbuminuria.

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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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Early Corneal Cellular and Nerve Fiber Pathology in Young Patients With Type 1 Diabetes Mellitus Identified Using Corneal Confocal Microscopy

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.15-18735 ◽

2016 ◽

Vol 57 (3) ◽

pp. 853 ◽

Cited By ~ 31

Author(s):

Eszter Szalai ◽

Eszter Deák ◽

László Módis ◽

Gábor Németh ◽

András Berta ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Confocal Microscopy ◽

Type 1 Diabetes Mellitus ◽

Nerve Fiber ◽

Young Patients ◽

Corneal Confocal Microscopy

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

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-319057 ◽

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.

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Corneal Confocal Microscopy Detects Early Nerve Regeneration After Pancreas Transplantation in Patients With Type 1 Diabetes

Diabetes Care ◽

10.2337/dc07-0870 ◽

2007 ◽

Vol 30 (10) ◽

pp. 2608-2612 ◽

Cited By ~ 154

Author(s):

S. Mehra ◽

M. Tavakoli ◽

P. A. Kallinikos ◽

N. Efron ◽

A. J.M. Boulton ◽

...

Keyword(s):

Type 1 Diabetes ◽

Confocal Microscopy ◽

Nerve Regeneration ◽

Pancreas Transplantation ◽

Corneal Confocal Microscopy

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Corneal confocal microscopy best identifies the development and progression of neuropathy in patients with type 1 diabetes

Journal of Diabetes and its Complications ◽

10.1016/j.jdiacomp.2017.04.025 ◽

2017 ◽

Vol 31 (8) ◽

pp. 1325-1327 ◽

Cited By ~ 9

Author(s):

Katie Edwards ◽

Nicola Pritchard ◽

Cirous Dehghani ◽

Dimitrios Vagenas ◽

Anthony Russell ◽

...

Keyword(s):

Type 1 Diabetes ◽

Confocal Microscopy ◽

Corneal Confocal Microscopy

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Corneal Confocal Microscopy Detects Neuropathy in Patients with Type 1 Diabetes without Retinopathy or Microalbuminuria

PLoS ONE ◽

10.1371/journal.pone.0123517 ◽

2015 ◽

Vol 10 (4) ◽

pp. e0123517 ◽

Cited By ~ 40

Author(s):

Ioannis N. Petropoulos ◽

Patrick Green ◽

Agnes W. S. Chan ◽

Uazman Alam ◽

Hassan Fadavi ◽

...

Keyword(s):

Type 1 Diabetes ◽

Confocal Microscopy ◽

Corneal Confocal Microscopy

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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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