scholarly journals Corneal Nerve Fiber Structure, Its Role in Corneal Function, and Its Changes in Corneal Diseases

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Hiroshi Eguchi ◽  
Akio Hiura ◽  
Hiroshi Nakagawa ◽  
Shunji Kusaka ◽  
Yoshikazu Shimomura
Keyword(s):  
Nerve Fiber ◽  
Trp Channels ◽  
Nerve Fibers ◽  
Corneal Epithelial Cell ◽  
Transient Receptor Potential Vanilloid ◽  
Eye Drops ◽  
Fiber Morphology ◽  
Corneal Nerves ◽  
Corneal Nerve ◽  
Neurotrophic Keratopathy

Recently, in vivo confocal microscopy is used to examine the human corneal nerve fibers morphology. Corneal nerve fiber architecture and its role are studied in healthy and pathological conditions. Corneal nerves of rats were studied by nonspecific acetylcholinesterase (NsAchE) staining. NsAchE-positive subepithelial (stromal) nerve fiber has been found to be insensitive to capsaicin. Besides, NsAchE-negative but capsaicin-sensitive subbasal nerve (leash) fibers formed thick mesh-like structure showing close interconnections and exhibit both isolectin B4- and transient receptor potential vanilloid channel 1- (TRPV1-) positive. TRPV1, TRPV3, TRPA (ankyrin) 1, and TRPM (melastatin) 8 are expressed in corneal nerve fibers. Besides the corneal nerve fibers, the expressions of TRPV (1, 3, and 4), TRPC (canonical) 4, and TRPM8 are demonstrated in the corneal epithelial cell membrane. The realization of the importance of TRP channels acting as polymodal sensors of environmental stresses has identified potential drug targets for corneal disease. The pathophysiological conditions of corneal diseases are associated with disruption of normal tissue innervation, especially capsaicin-sensitive small sensory nerve fibers. The relationships between subbasal corneal nerve fiber morphology and neurotrophic keratopathy in corneal diseases are well studied. The recommended treatment for neurotrophic keratopathy is administration of preservative free eye drops.

scholarly journals Early detection of diabetic neuropathy by investigating CNFL and IENFD in thy1-YFP mice

2016 ◽  
Vol 231 (2) ◽  
pp. 147-157 ◽  
Author(s):  
Janine Leckelt ◽  
Pedro Guimarães ◽  
Annett Kott ◽  
Alfredo Ruggeri ◽  
Oliver Stachs ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Nerve Fiber ◽  
Blood Glucose Concentration ◽  
Ex Vivo ◽  
Surrogate Marker ◽  
Nerve Fibers ◽  
Fiber Density ◽  
Corneal Confocal Microscopy ◽  
Intraepidermal Nerve Fiber Density ◽  
Corneal Nerve

Small fiber neuropathy is one of the most common and painful long-term complications of diabetes mellitus. Examination of the sub-basal corneal nerve plexus is a promising surrogate marker of diabetic neuropathy. To investigate the efficacy, reliability and reproducibility of in vivo corneal confocal microscopy (IVCCM), we used thy1-YFP mice, which express yellow fluorescence protein (YFP) in nerve fibers. 4 weeks after multiple low-dose injections of streptozotocin, thy1-YFP mice showed manifest diabetes. Subsequent application of insulin-releasing pellets for 8 weeks resulted in a significant reduction of blood glucose concentration and HbA1c, a significant increase in body weight and no further increase in advanced glycation end products (AGEs). IVCCM, carried out regularly over 12 weeks and analyzed both manually and automatically, revealed a significant loss of corneal nerve fiber length (CNFL) during diabetes manifestation and significant recovery after insulin therapy. Ex vivo analyses of CNFL by YFP-based microscopy confirmed the IVCCM results (with high sensitivity between manual and automated approaches) but demonstrated that the changes were restricted to the central cornea. Peripheral areas, not accessible by IVCCM in mice, remained virtually unaffected. Because parallel assessment of intraepidermal nerve fiber density revealed no changes, we conclude that IVCCM robustly captures early signs of diabetic neuropathy.

scholarly journals Corneal Subbasal Nerve Recovery in an Acute Case of Ultraviolet Keratitis Treated with Autologous Serum Eye Drops

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Farshad Abedi ◽  
Pedram Hamrah
Keyword(s):  
Laser Scanning ◽  
Ophthalmic Solution ◽  
Autologous Serum ◽  
Eye Drops ◽  
Blurred Vision ◽  
Acute Case ◽  
Corneal Nerves ◽  
Corneal Nerve ◽  
Uv C ◽  
Serum Eye Drops

Purpose. To report degeneration of subbasal corneal nerves and the subsequent neuroregeneration in a case of acute ultraviolet (UV) keratitis, treated with autologous serum eye drops. Methods. Case report. Results. A 37-year-old female presented with ocular discomfort and blurred vision in both eyes, after exposure to UV-C light in a laboratory. On exam, she had bilateral conjunctival injection and superficial punctate keratitis (SPK), worse in the left, consistent with acute, bilateral, but asymmetric UV-C keratitis. She was initially started on antibiotic ointment and lubricant eye drops. On her follow-up visit 3 days later, corneas had persistent SPK bilaterally. Laser scanning in vivo confocal microscopy (IVCM) showed beading of subbasal corneal nerves in the right eye and decreased subbasal corneal nerve density and numerous amputated nerves in the left eye. Autologous serum eye drops 20%, eight times a day, and loteprednol 0.5% ophthalmic solution were commenced in both eyes. Twelve weeks later, her symptoms fully resolved; IVCM revealed near-normal subbasal corneal nerve density in both eyes. Conclusions. IVCM demonstrated dramatic damage to subbasal corneal nerves after brief UV-C exposure. The patient, treated with autologous serum eye drops in both eyes, achieved resolution of symptoms and recovery of subbasal corneal nerves.

scholarly journals Automatic corneal nerve fiber segmentation and geometric biomarker quantification

2020 ◽  
Vol 135 (2) ◽  
Author(s):  
Dan Zhang ◽  
Fan Huang ◽  
Maziyar Khansari ◽  
Tos T. J. M. Berendschot ◽  
Xiayu Xu ◽  
...  
Keyword(s):  
Nerve Fiber ◽  
Extraction Methods ◽  
Nerve Fibers ◽  
Convolutional Network ◽  
Fiber Network ◽  
Fiber Extraction ◽  
Topological Features ◽  
Corneal Nerve ◽  
Fully Automatic ◽  
Microscopy Images

Abstract Geometric and topological features of corneal nerve fibers in confocal microscopy images are important indicators for the diagnosis of common diseases such as diabetic neuropathy. Quantitative analysis of these important biomarkers requires an accurate segmentation of the nerve fiber network. Currently, most of the analysis are performed based on manual annotations of the nerve fiber segments, while a fully automatic corneal nerve fiber extraction and analysis framework is still needed. In this paper, we establish a fully convolutional network method to precisely enhance and segment corneal nerve fibers in microscopy images. Based on the segmentation results, automatic tortuosity measurement and branching detection modules are established to extract valuable geometric and topological biomarkers. The proposed segmentation method is validated on a dataset with 142 images. The experimental results show that our deep learning-based framework outperforms state-of-the-art segmentation approaches. The biomarker extraction methods are validated on two different datasets, demonstrating high effectiveness and reliability of the proposed methods.

Characterization of small nerve fibers in painful distal symmetric polyneuropathy and healthy controls

2015 ◽  
Vol 8 (1) ◽  
pp. 51
Author(s):  
P. Karlsson ◽  
S. Haroutounian ◽  
M. Polydefkis ◽  
J.R. Nyengaard ◽  
T.S. Jensen
Keyword(s):  
Nerve Fiber ◽  
Quantitative Sensory Testing ◽  
Nerve Fibers ◽  
Healthy Controls ◽  
Sensory Testing ◽  
Fiber Morphology ◽  
Small Fiber ◽  
Intraepidermal Nerve Fiber Density ◽  
Distal Symmetric Polyneuropathy ◽  
Small Nerve

AbstractAimsThe introduction of skin biopsies to examine small nerve fiber morphology together with functional measures such as quantitative sensory testing (QST) has led to an improvement in diagnosing patients with small fiber neuropathy (SFN). Quantification of intraepidermal nerve fiber density (IENFD) is an important measure in SFN. However, the relationship between structure and function is not straightforward and the morphological and functional fiber characteristics are still unclear. This study aimed to combine structural and functional measurements to improve the diagnosis of distal symmetric polyneuropathy and small fiber involvement. Additionally, we investigated whether patients and healthy controls have differential patterns of correlations between structural and functional nerve measurements.Methods17 patients with painful distal symmetric polyneu-ropathy (DSP) and 19 controls underwent comprehensive small fiber assessments that included quantitative sensory testing, response to topical capsaicin and analysis of skin biopsy samples (IENFD, epidermal and dermal nerve fiber length densities (eNFLD, dNFLD) and swellings).ResultsDSP patients had reduced sensitivity to cold and heat, diminished capsaicin response, and lower IENFD, eNFLD and dNFLD (all p < 0.0003).The correlation between structural and functional parameters was better in controls than in DSP. A diagnostic approach of combined IENFD and eNFLD utilization, increased DSP diagnostic sensitivity from 82.0% to 100% and specificity from 84.0% to 89.5%.ConclusionsA correlation is found between functional and structural small fiber parameters for DSP and controls, and an approach to improve diagnostic accuracy in DSP is suggested.

scholarly journals Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology

2021 ◽  
Vol 2 ◽  
Author(s):  
Ioannis N. Petropoulos ◽  
Gulfidan Bitirgen ◽  
Maryam Ferdousi ◽  
Alise Kalteniece ◽  
Shazli Azmi ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Diabetic Neuropathy ◽  
Nerve Fiber ◽  
Clinical Intervention ◽  
Nerve Fibers ◽  
Fiber Density ◽  
Corneal Confocal Microscopy ◽  
Intraepidermal Nerve Fiber Density ◽  
Corneal Nerve ◽  
Small Nerve

Neuropathic pain has multiple etiologies, but a major feature is small fiber dysfunction or damage. Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that can image small nerve fibers in the cornea and has been utilized to show small nerve fiber loss in patients with diabetic and other neuropathies. CCM has comparable diagnostic utility to intraepidermal nerve fiber density for diabetic neuropathy, fibromyalgia and amyloid neuropathy and predicts the development of diabetic neuropathy. Moreover, in clinical intervention trials of patients with diabetic and sarcoid neuropathy, corneal nerve regeneration occurs early and precedes an improvement in symptoms and neurophysiology. Corneal nerve fiber loss also occurs and is associated with disease progression in multiple sclerosis, Parkinson's disease and dementia. We conclude that corneal confocal microscopy has good diagnostic and prognostic capability and fulfills the FDA criteria as a surrogate end point for clinical trials in peripheral and central neurodegenerative diseases.

scholarly journals Augmented Corneal Nerve Fiber Branching in Painful Compared With Painless Diabetic Neuropathy

2019 ◽  
Vol 104 (12) ◽  
pp. 6220-6228
Author(s):  
Sonja Püttgen ◽  
Gidon J Bönhof ◽  
Alexander Strom ◽  
Karsten Müssig ◽  
Julia Szendroedi ◽  
...  
Keyword(s):  
Nerve Fiber ◽  
Rating Scale ◽  
Nerve Fibers ◽  
Control Group ◽  
Fiber Density ◽  
Nerve Branch ◽  
Perception Threshold ◽  
Cross Sectional ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

AbstractContextThe factors that determine the development of diabetic sensorimotor polyneuropathy (DSPN) as a painful or painless entity are unknown.ObjectiveWe hypothesized that corneal nerve pathology could be more pronounced in painful DSPN, indicating predominant small nerve fiber damage.Design and MethodsIn this cross-sectional study, we assessed 53 patients with painful DSPN, 63 with painless DSPN, and 46 glucose-tolerant volunteers by corneal confocal microscopy (CCM), nerve conduction (NC), and quantitative sensory testing. DSPN was diagnosed according to modified Toronto Consensus criteria. A cutoff at 4 points on the 11-point rating scale was used to differentiate between painful and painless DSPN.ResultsAfter adjustment for age, sex, body mass index, and smoking, corneal nerve fiber density, corneal nerve fiber length, and corneal nerve branch density (CNBD) were reduced in both DSPN types compared with the control group (P < 0.05). Only CNBD differed between the groups; it was greater in patients with painful DSPN compared with those with painless DSPN [55.8 (SD, 29.9) vs 43.8 (SD, 28.3) branches/mm2; P < 0.05]. Several CCM measures were associated with NC and cold perception threshold in patients with painless DSPN (P < 0.05) but not those with painful DSPN.ConclusionDespite a similarly pronounced peripheral nerve dysfunction and corneal nerve fiber loss in patients with painful and painless DSPN, corneal nerve branching was enhanced in those with painful DSPN, pointing to some susceptibility of corneal nerve fibers toward regeneration in this entity, albeit possibly not to a sufficient degree.

scholarly journals Automatic Tortuosity Estimation of Nerve Fibers and Retinal Vessels in Ophthalmic Images

2020 ◽  
Vol 10 (14) ◽  
pp. 4788
Author(s):  
Honghan Chen ◽  
Bang Chen ◽  
Dan Zhang ◽  
Jiong Zhang ◽  
Jiang Liu ◽  
...  
Keyword(s):  
Nerve Fiber ◽  
Estimation Method ◽  
Weighted Average ◽  
Retinal Vessel ◽  
Ground Truth ◽  
Nerve Fibers ◽  
Public Access ◽  
Close Relationship ◽  
Enhancement Method ◽  
Corneal Nerve

The tortuosity changes of curvilinear anatomical organs such as nerve fibers or vessels have a close relationship with a number of diseases. Therefore, the automatic estimation and representation of the tortuosity is desired in medical image for such organs. In this paper, an automated framework for tortuosity estimation is proposed for corneal nerve and retinal vessel images. First, the weighted local phase tensor-based enhancement method is employed and the curvilinear structure is extracted from raw image. For each curvilinear structure with a different position and orientation, the curvature is measured by the exponential curvature estimation in the 3D space. Then, the tortuosity of an image is calculated as the weighted average of all the curvilinear structures. Our proposed framework has been evaluated on two corneal nerve fiber datasets and one retinal vessel dataset. Experiments on three curvilinear organ datasets demonstrate that our proposed tortuosity estimation method achieves a promising performance compared with other state-of-the-art methods in terms of accuracy and generality. In our nerve fiber dataset, the method achieved overall accuray of 0.820, and 0.734, 0.881 for sensitivity and specificity, respectively. The proposed method also achieved Spearman correlation scores 0.945 and 0.868 correlated with tortuosity grading ground truth for arteries and veins in the retinal vessel dataset. Furthermore, the manual labeled 403 corneal nerve fiber images with different levels of tortuosity, and all of them are also released for public access for further research.

scholarly journals Oral Aminoacids Supplementation Improves Corneal Reinnervation After Photorefractive Keratectomy: A Confocal-Based Investigation

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna M Roszkowska ◽  
Dario Rusciano ◽  
Leandro Inferrera ◽  
Alice Antonella Severo ◽  
Pasquale Aragona
Keyword(s):  
Topical Therapy ◽  
Sodium Hyaluronate ◽  
Nerve Fibers ◽  
Photorefractive Keratectomy ◽  
Control Group ◽  
Oral Supplementation ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerves ◽  
Corneal Nerve

Aim of this retrospective study was to estimate the effect of oral supplementation with amino acids (AA) on corneal nerves regrowth after excimer laser refractive surgery with photorefractive keratectomy (PRK). Based on the pre and post-surgical treatment received, 40 patients with 12 months of follow-up were distributed in two groups: 20 patients had received oral AA supplementation 7 days before and 30 days after PRK, and 20 patients without AA supplementation, as untreated reference control. All patients followed the same standard post-operative topical therapy consisting of an association of antibiotic and steroid plus sodium hyaluronate during the first week, then steroid alone progressively decreasing during 30 days and sodium hyaluronate for the following 3 months. In vivo corneal confocal microscopy was used to evaluate the presence of sub-basal corneal nerve fibers during 12 months after PRK. Results have shown that sub-basal nerves regenerated significantly faster (p &lt;0.05), and nerve fibers density was significantly higher (p &lt;0.05) with a more regular pattern in the eyes of AA treated patients with respect to the untreated control group. Therefore, our data indicate that oral supplementation with AA improved significantly corneal nerve restoration after PRK and could thus be considered as an additional treatment during corneal surgical procedures.

Effects of Shumu Decoction on Pathological Changes of Cornea in Patients with Diabetic Dry Eye

2020 ◽  
Author(s):  
hua zhi han ◽  
Wen-Juan Wei ◽  
Sheng-Jun Tuo ◽  
Wu-Feng Zhang
Keyword(s):  
Treatment Group ◽  
Dry Eye ◽  
Langerhans Cells ◽  
Corneal Thickness ◽  
Nerve Fibers ◽  
Corneal Epithelial Cell ◽  
Control Group ◽  
Eye Drops ◽  
Pathological Changes ◽  
Significant Difference

Abstract BACKGROUND:To observe the pathological changes of cornea and to clarify the effect Shumu Decoction on the cornea in diabetic dry eye.METHODS:The study assessed 200 eyes of 100 patients with diabetic dry eye.The treatment group 50 patients(100 eyes) and the control group 50 patients(100 eyes). The control group was treated with sodium hyaluronate eye drops. On the basis of the control group, the treatment group was treated by oral administration of Shumu Decoction.All participants underwent the examination of laser confocal microscope to obtain the image of cornea which were used to evaluate the differences between the two groups before and after treatment.RESULTS:After treatment,The corneal epithelial cell density in the treatment group was significantly higher than that in the control group(P <0.05) .The cell area of the two groups increased compared with that before treatment, but the area in the control group was significantly larger than that in the treatment group (P<0.05).The number of Langerhans cells in the control group were significantly higher than that in the treatment group(P<0.05).The morphology of Langerhans cells was characterized by large area and pseudopodia in the control group.The density, length of central corneal nerve fibers in the two groups were reduced compared to before treatment, but the decrease of nerve fiber in the control group was more obvious than that in the treatment group(P<0.05), and the morphology of nerve fibers was obvious change in the control group(P<0.05).At 4 weeks' treatment,the corneal endothelial cells showed morphological abnormality, there was significant difference in the ratio of endothelial cell hexagon between the two groups, and the corneal thickness increased significantly in the control group(P<0.05).CONCLUSION:Shumu Decoction can delay the loss of corneal cells and nerve fibers and restore the normal function of cornea.Those changes may alleviate the symptoms of patients with diabetic dry eye

scholarly journals Assessment and comparison of the morphology and function of the corneal sub-basal nerve plexus in type-1 diabetes mellitus patients and in healthy subjects

2016 ◽  
Vol 1 (1) ◽  
pp. 51-63
Author(s):  
Irmante Derkac ◽  
Ingrida Januleviciene ◽  
Kirwan Asselineau ◽  
Dzilda Velickiene
Keyword(s):  
Nerve Fiber ◽  
Healthy Subjects ◽  
Nerve Fibers ◽  
Corneal Sensitivity ◽  
Fiber Density ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve ◽  
Type 1 Dm ◽  
Nerve Fiber Density

Aim/purpose: It is believed that small nerve bundles are damaged in the earliest stages of neuropathy caused by diabetes mellitus (DM). Our goal was to evaluate and compare anatomical characteristics of corneal nerve fibers and corneal sensitivity in type-1 DM patients and in healthy control subjects.Design: A prospective, masked, controlled cross-sectional clinical study.Method: Thirty patients with type-1 DM and ten non-diabetic healthy subjects underwent a corneal confocal microscopy to evaluate the corneal sub-basal nerve fibers (density, number of nerves and branches, total nerve length) and contact corneal esthesiometry.Results: Diabetic patients had significantly lower corneal nerve fiber density density (14.32 ± 5.87 vs. 19.71 ± 5.59 mm/mm2; p = 0.023 ) nerve branches number (4.57 ± 3,91 vs. 9.90 ± 5.8 n°/image; p = 0.006) , nerve fiber length (2.28 ± 0.94 vs. 3.13 ± 0.89 mm; p = 0.032) and corneal sensitivity (1.13 ± 0.29 vs. 0.98 ± 0.058 gr/mm2 p = 0.02), as compared with controls. A negative correlation was found between corneal nerve fiber length, corneal nerve number, corneal nerve fiber density and disease duration (p < 0.05).Conclusion: Corneal confocal microscopy and corneal sensitivity evaluation are noninvasive techniques helping to detect early changes in the sub-basal nerve plexus characteristic for diabetic neuropathy (DN) in patients with type-1 DM. Further studies are required to investigate the role of corneal neuropathy assessment using these novel techniques as a toll to detect early DN. 

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