Association of corneal nerve fiber measures with cognitive function in dementia

AbstractCognitive impairment in Parkinson’s disease (PD) adversely influences quality of life. There is currently no available biomarker to predict cognitive decline in PD. Corneal confocal microscopy (CCM) has been used as a non-invasive tool for quantifying small nerve damage in PD. The present study investigated whether corneal nerve measures were associated with cognitive function in PD. Patients with PD were classified into those with normal cognitive function (PD-CN), mild cognitive impairment (PD-MCI), and dementia (PDD). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were quantified with CCM and compared with a control group. Sixty-five PD patients and thirty controls were studied. CNFD was decreased and CNBD was increased in PD patients compared to controls (P < 0.05). CNBD and CNBD/CNFD ratio was higher in PD-CN compared to controls. CNFD was positively correlated with the Montreal cognitive assessment (MoCA) score (r = 0.683, P < 0.001), but negatively associated with unified Parkinson disease rating scale (UPDRS)-part III (r = −0.481, P < 0.001) and total UPDRS scores (r = −0.401, P = 0.001) in PD patients. There was no correlation between CNFD and Levodopa equivalent daily dose (LEDD) (r = 0.176, P = 0.161). CNFD, CNBD, CNFL, and CNBD/CNFD ratio was lower with increasing Hoehn and Yahr stage. PD patients show evidence of corneal nerve loss compared with controls and corneal nerve parameters are associated with the severity of cognitive and motor dysfunction in PD. CCM could serve as an objective in vivo ophthalmic imaging technique to assess neurodegeneration in PD.

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Corneal Nerve Fiber Loss Relates to Cognitive Impairment in Patients with Parkinson’s Disease

10.21203/rs.3.rs-112941/v1 ◽

2020 ◽

Author(s):

Ning-Ning Che ◽

Qiu-Huan Jiang ◽

Guan-Xiao Ding ◽

Si-Yuan Chen ◽

Zhen-Xiang Zhao ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Cognitive Function ◽

Nerve Fiber ◽

Rating Scale ◽

Motor Dysfunction ◽

Control Group ◽

Corneal Confocal Microscopy ◽

Corneal Nerve

Abstract Background Cognitive impairment in Parkinson’s disease (PD) adversely influences quality of life. There is currently no available biomarker to predict cognitive decline in PD. PD involves both the central and peripheral nervous system and especially small fiber damage occurs in PD. Corneal confocal microscopy (CCM) has been used as a non-invasive tool for quantifying small nerve fibre damage in PD. The present study investigated whether corneal nerve measures were associated with cognitive function in PD. Methods Patients with PD were classified into those with normal cognitive function (PD-CN), mild cognitive impairment (PD-MCI), and dementia (PDD). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) were quantified with CCM and compared with a control group.Results Sixty-five PD patients (44.62% male; mean age 64.60±6.95 years; mean disease duration 4.63±2.53 years) and 30 controls (53.33% male; mean age 62.43±6.16 years) were studied. CNFD was decreased and CNBD was increased in PD patients compared to controls ( P <0.05). CNFD decreased progressively with decline in cognitive function in PD patients. CNBD and CNBD/CNFD ratio was higher in PD-CN compared to controls but decreased with worsening cognitive function in PD-MCI and PDD patients. CNFD correlated with the Montreal cognitive assessment (MoCA) score ( r =0.683, P <0.0001), unified Parkinson disease rating scale (UPDRS)-part III ( r =-0.481, P <0.0001) and total UPDRS scores ( r =-0.401, P <0.0001) in PD patients. CNFD, CNBD, CNFL were lower and CNBD/CNFD ratio was higher with increasing Hoehn and Yahr stage. There was no correlation between CNFD and Levodopa equivalent daily dose (LEDD) ( r =0.176, P =0.161). CNFD, CNBD and CNFL could discriminate between PD-MCI and PD-CN with an area under the curve (AUC) of 82.85%, 67.47%, and 78.74%, respectively. CNFD, CNBD and CNFL could discriminate between PDD and PD-CN with an AUC of 96.67%, 90.12% and 84.44%. A combination of all three CCM parameters further increased the AUC value. Conclusions PD patients show evidence of corneal nerve loss compared with controls and corneal nerve parameters are associated with the severity of cognitive and motor dysfunction in PD. CCM could serve as an objective in vivo ophthalmic imaging technique to assess neurodegeneration in PD.

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Faculty Opinions recommendation of Correlation between sudomotor function, sweat gland duct size and corneal nerve fiber pathology in patients with type 2 diabetes mellitus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718204748.793488266 ◽

2013 ◽

Author(s):

Rayaz Malik

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Nerve Fiber ◽

Sweat Gland ◽

Sudomotor Function ◽

Gland Duct ◽

Corneal Nerve

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An In Vivo Confocal Microscopic Study of Corneal Nerve Morphology in Unilateral Keratoconus

BioMed Research International ◽

10.1155/2016/5067853 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 7

Author(s):

Natasha Kishore Pahuja ◽

Rohit Shetty ◽

Rudy M. M. A. Nuijts ◽

Aarti Agrawal ◽

Arkasubhra Ghosh ◽

...

Keyword(s):

Nerve Fiber ◽

Nerve Branch ◽

Intergroup Comparison ◽

Corneal Nerve ◽

Group 3 ◽

Group 2 ◽

Branch Density ◽

Corneal Nerve Morphology ◽

Group 1

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

Cornea ◽

10.1097/ico.0000000000002836 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Osman Ahmet Polat ◽

Hidayet Şener ◽

Kuddusi Erkiliç

Keyword(s):

Nerve Fiber ◽

Sensitivity Loss ◽

Anti Vegf ◽

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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