Corneal Nerve Fiber and Sensitivity Loss After Repeated Intravitreal Anti-VEGF Injections

Purpose.To study the corneal nerve morphology and its importance in unilateral keratoconus.Materials and Methods.In this prospective cross-sectional study, 33 eyes of 33 patients with keratoconus in one eye (Group 3) were compared with the other normal eye of the same patients (Group 2) and 30 eyes of healthy patients (Group 1). All patients underwent detailed ophthalmic examination followed by topography with Pentacam HR and in vivo confocal microscopy (IVCM). Five images obtained with IVCM were analyzed using an automated CCmetrics software version 1.0 for changes in subbasal plexus of nerves.Results.Intergroup comparison showed statistically significant reduction in corneal nerve fiber density (CNFD) and length (CNFL) in Group 3 as compared to Group 1 (p<0.001andp=0.001, resp.) and Group 2 (p=0.01andp=0.02, resp.). Though corneal nerve fiber length, diameter, area, width, corneal nerve branch density, and corneal total branch density were found to be higher in decentered cones, only the corneal nerve branch density (CNBD) was found to be statistically significant (p<0.01) as compared to centered cones.Conclusion.Quantitative changes in the corneal nerve morphology can be used as an imaging marker for the early diagnosis of keratoconus before the onset of refractive or topography changes.

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S cone pathway sensitivity loss in ocular hypertension and early glaucoma has nerve fiber bundle pattern

Documenta Ophthalmologica Proceedings Series - Colour Vision Deficiencies X ◽

10.1007/978-94-011-3774-4_65 ◽

1991 ◽

pp. 535-542 ◽

Cited By ~ 3

Author(s):

Anthony J. Adams ◽

Chris A. Johnson ◽

Richard A. Lewis

Keyword(s):

Ocular Hypertension ◽

Nerve Fiber ◽

Fiber Bundle ◽

Early Glaucoma ◽

Sensitivity Loss ◽

Cone Pathway

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P4-339: ASSOCIATION OF CORNEAL NERVE FIBER MEASURES WITH COGNITIVE FUNCTION IN DEMENTIA

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.4009 ◽

2019 ◽

Vol 15 ◽

pp. P1427-P1428

Author(s):

Georgios Ponirakis ◽

Hanadi Al Hamad ◽

Anoop Sankaranarayanan ◽

Adnan Khan ◽

Mani Chandran ◽

...

Keyword(s):

Cognitive Function ◽

Nerve Fiber ◽

Corneal Nerve

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Erratum to: ARA 290 Improves Symptoms in Patients with Sarcoidosis-Associated Small Nerve Fiber Loss and Increases Corneal Nerve Fiber Density

Molecular Medicine ◽

10.2119/molmed.2013.00122.erratum ◽

2016 ◽

Vol 22 (1) ◽

pp. 674-674

Author(s):

Albert Dahan ◽

Ann Dunne ◽

Maarten Swartjes ◽

Paolo L. Proto ◽

Lara Heij ◽

...

Keyword(s):

Nerve Fiber ◽

Fiber Density ◽

Corneal Nerve ◽

Nerve Fiber Density ◽

Small Nerve

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Corneal nerve quantification predicts the severity of symptoms in sarcoidosis patients with painful neuropathy

TECHNOLOGY ◽

10.1142/s2339547813500039 ◽

2013 ◽

Vol 01 (01) ◽

pp. 20-26 ◽

Cited By ~ 6

Author(s):

M. Brines ◽

M. Swartjes ◽

M.R. Tannemaat ◽

A. Dunne ◽

M. van Velzen ◽

...

Keyword(s):

Nerve Fiber ◽

Adult Population ◽

Brief Pain Inventory ◽

The United States ◽

Fiber Density ◽

Painful Neuropathy ◽

Small Fiber ◽

Corneal Confocal Microscopy ◽

Fiber Number ◽

Corneal Nerve

Small fiber neuropathy (SFN) is a debilitating condition characterized by chronic pain as well as sensory and autonomic dysfunction. SFN is an increasingly recognized component of a large number of diseases, including sarcoidosis. Although affecting an estimated 2–3% of the adult population in the United States, it often remains undiagnosed. Skin biopsy for evaluating intra-epidermal nerve fiber density (IENFD) and more recently corneal confocal microscopy (CCM) have been used to identify small fiber damage in patients with neuropathy. We demonstrate a significant reduction in IENFD, corneal nerve fiber number and length, with no change in the number of branches in patients with painful sarcoid neuropathy. Moreover, unlike IENFD, corneal nerve fiber number and length inversely correlate with the degree to which pain interferes with activities of daily living as assessed by the Brief Pain Inventory questionnaire. CCM thus constitutes an accurate, non-invasive assessment technique to aid in the diagnosis of SFN, as well as an objective marker of symptoms in patients with painful sarcoid neuropathy.

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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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Pathogenic role of PPARα down-regulation in corneal nerve degeneration and impaired corneal sensitivity in diabetes

10.2337/db20-4567/suppl.12000825.v1 ◽

2020 ◽

Author(s):

Ada Admin ◽

Greg Matlock ◽

Fangfang Qiu ◽

Volha Malechka ◽

Kelu Zhou ◽

...

Keyword(s):

Nerve Fiber ◽

Diabetic Rats ◽

Nerve Degeneration ◽

Diabetic Mice ◽

Corneal Sensitivity ◽

Fenofibrate Treatment ◽

Corneal Nerve ◽

Rats And Mice ◽

Diabetic Keratopathy

The purpose of this study was to investigate the protective role of Peroxisome Proliferator‐Activated Receptor‐alpha (PPARα) against diabetic keratopathy and corneal neuropathy. Corneal samples were obtained from diabetic and non-diabetic human donors. Streptozotocin-induced diabetic rats and mice were orally treated with PPARα agonist fenofibrate. As shown by immunohistochemistry and Western blotting, PPARα was down-regulated in the corneas of diabetic humans and rats. Immunostaining of β-III tubulin demonstrated that corneal nerve fiber metrics were decreased significantly in diabetic rats and mice, which was partially prevented by fenofibrate treatment. As evaluated using a Cochet-Bonnet aesthesiometer, corneal sensitivity was significantly decreased in diabetic mice, which was prevented by fenofibrate. PPARα-/- mice displayed progressive decreases in the corneal nerve fiber density. Consistently, corneal sensitivity was decreased in PPARα-/- mice relative to wild-type mice by nine months of age. Diabetic mice showed increased incidence of spontaneous corneal epithelial lesion, which was prevented by fenofibrate while exacerbated by PPARα knockout. Western blot analysis revealed significantly altered neurotrophic factor levels in diabetic rat corneas, which were partially restored by fenofibrate treatment. These results indicate that PPARα protects corneal nerve from degeneration induced by diabetes, and PPARα agonists have therapeutic potential in the treatment of diabetic keratopathy.

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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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