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Optic neuritis (ON), a demyelinating disease of the central nervous system, is often a precursor manifestation of neuromyelitis optica spectrum disorders (NMOSD) or multiple sclerosis (MS). Reduced corneal nerve fiber counts have been found in patients with NMOSD or MS. This study aimed to observe and compare the corneal subbasal nerve plexus in patients with three types of ON and controls without ON using in vivo corneal confocal microscopy (IVCM). Data were analyzed for 77 eyes of 48 patients with ON, grouped according to seropositivity for anti-aquaporin-4 IgG, myelin oligodendrocyte glycoprotein antibody, or no seropositivity, and 35 healthy eyes in the control group. Corneal parameters were quantified based on IVCM images. Visual function indicators were recorded, following which their correlations with IVCM parameters were analyzed. Significant differences in IVCM parameters were detected among the different groups. Reductions in corneal nerve fiber counts were negatively correlated with visual acuity. Corneal nerve fibers were significantly more damaged in the affected eye than in the unaffected eye in patients with ON. IVCM revealed corneal nerve fiber loss of varying degrees, depending on the type of ON. This indicates that, although ON primarily affects the central nervous system, peripheral nerves, such as the trigeminal nerve, which innervates the corneal subbasal nerve plexus may also be damaged in affected patients. [ABSTRACT FROM AUTHOR]

Corneal nerve homeostasis is essential for the functional integrity of the ocular surface. Vitamin D deficiency (VDD) and vitamin D receptor knockout (VDR KO) have been found to reduce corneal nerve density in diabetic mice. This is the first study to comprehensively examine the influence of vitamin D on nerve regeneration following corneal epithelial injury in diabetic mice. Corneal nerve regeneration was significantly retarded by diabetes, VDR KO, and VDD, and it was accelerated following topical 1,25 Vit D and 24,25 Vit D administration. Furthermore, topical 1,25 Vit D and 24,25 Vit D increased nerve growth factor, glial cell line-derived neurotropic factor, and neurotropin-3 protein expression, and it increased secretion of GDNF protein from human corneal epithelial cells. CD45+ cells and macrophage numbers were significantly decreased, and vitamin D increased CD45+ cell and macrophage recruitment in these wounded diabetic mouse corneas. The accelerated nerve regeneration observed in these corneas following topical 1,25 Vit D and 24,25 Vit D administration may be related to the vitamin D-stimulated expression, secretion of neurotrophic factors, and recruitment of immune cells. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a heterogeneous movement disorder with patients manifesting with either tremor-dominant (TD) or postural instability and gait disturbance (PIGD) motor subtypes. Small nerve fiber damage occurs in patients with PD and may predict motor progression, but it is not known whether it differs between patients with different motor subtypes. Objective: The aim of this study was to explore whether there was an association between the extent of corneal nerve loss and different motor subtypes. Methods: Patients with PD classified as TD, PIGD, or mixed subtype underwent detailed clinical and neurological evaluation and corneal confocal microscopy (CCM). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were compared between groups, and the association between corneal nerve fiber loss and motor subtypes was investigated. Results: Of the 73 patients studied, 29 (40%) had TD, 34 (46%) had PIGD, and 10 (14%) had a mixed subtype. CNFD (no./mm2, 24.09 ± 4.58 versus 28.66 ± 4.27; p < 0.001), CNBD (no./mm2, 28.22 ± 11.11 versus 37.37 ± 12.76; p = 0.015), and CNFL (mm/mm2, 13.11 ± 2.79 versus 16.17 ± 2.37; p < 0.001) were significantly lower in the PIGD group compared with the TD group. Multivariate logistic regression showed that higher CNFD (OR = 1.265, p = 0.019) and CNFL (OR = 1.7060, p = 0.003) were significantly associated with the TD motor subtype. The receiver operating characteristic (ROC) analysis demonstrated that combined corneal nerve metrics showed excellent discrimination between TD and PIGD, with an area under the curve (AUC) of 0.832. Conclusion: Greater corneal nerve loss occurs in patients with PIGD compared with TD, and patients with a higher CNFD or CNFL were more likely to have the TD subtype. CCM may have clinical utility in differentiating different motor subtypes in PD. [ABSTRACT FROM AUTHOR]

Corneal nerve homeostasis is essential for the functional integrity of the ocular surface. Vitamin D deficiency (VDD) and vitamin D receptor knockout (VDR KO) have been found to reduce corneal nerve density in diabetic mice. This is the first study to comprehensively examine the influence of vitamin D on nerve regeneration following corneal epithelial injury in diabetic mice. Corneal nerve regeneration was significantly retarded by diabetes, VDR KO, and VDD, and it was accelerated following topical 1,25 Vit D and 24,25 Vit D administration. Furthermore, topical 1,25 Vit D and 24,25 Vit D increased nerve growth factor, glial cell line-derived neurotropic factor, and neurotropin-3 protein expression, and it increased secretion of GDNF protein from human corneal epithelial cells. CD45+ cells and macrophage numbers were significantly decreased, and vitamin D increased CD45+ cell and macrophage recruitment in these wounded diabetic mouse corneas. The accelerated nerve regeneration observed in these corneas following topical 1,25 Vit D and 24,25 Vit D administration may be related to the vitamin D-stimulated expression, secretion of neurotrophic factors, and recruitment of immune cells.

Background: Parkinson's disease (PD) is a heterogeneous movement disorder with patients manifesting with either tremor-dominant (TD) or postural instability and gait disturbance (PIGD) motor subtypes. Small nerve fiber damage occurs in patients with PD and may predict motor progression, but it is not known whether it differs between patients with different motor subtypes. Objective: The aim of this study was to explore whether there was an association between the extent of corneal nerve loss and different motor subtypes. Methods: Patients with PD classified as TD, PIGD, or mixed subtype underwent detailed clinical and neurological evaluation and corneal confocal microscopy (CCM). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were compared between groups, and the association between corneal nerve fiber loss and motor subtypes was investigated. Results: Of the 73 patients studied, 29 (40%) had TD, 34 (46%) had PIGD, and 10 (14%) had a mixed subtype. CNFD (no./mm2, 24.09 ± 4.58 versus 28.66 ± 4.27; p < 0.001), CNBD (no./mm², 28.22 ± 11.11 versus 37.37 ± 12.76; p = 0.015), and CNFL (mm/mm², 13.11 ± 2.79 versus 16.17 ± 2.37; p < 0.001) were significantly lower in the PIGD group compared with the TD group. Multivariate logistic regression showed that higher CNFD (OR = 1.265, p = 0.019) and CNFL (OR = 1.7060, p = 0.003) were significantly associated with the TD motor subtype. The receiver operating characteristic (ROC) analysis demonstrated that combined corneal nerve metrics showed excellent discrimination between TD and PIGD, with an area under the curve (AUC) of 0.832. Conclusion: Greater corneal nerve loss occurs in patients with PIGD compared with TD, and patients with a higher CNFD or CNFL were more likely to have the TD subtype. CCM may have clinical utility in differentiating different motor subtypes in PD. [ABSTRACT FROM AUTHOR]

Objective. Corneal nerve fiber (CNF) has been found to exhibit morphological changes associated with various diseases, which can therefore be utilized to aid in the early diagnosis of those diseases. CNF is usually visualized under corneal confocal microscopy (CCM) in clinic. To obtain the diagnostic biomarkers from CNF image produced from CCM, image processing and quantitative analysis are needed. Usually, CNF is segmented first and then CNF’s centerline is extracted, allowing for measuring geometrical and topological biomarkers of CNF, such as density, tortuosity, and length. Consequently, the accuracy of the segmentation and centerline extraction can make a big impact on the biomarker measurement. Thus, this study is aimed to improve the accuracy and universality of centerline extraction. Approach. We developed a new thinning algorithm based on neighborhood statistics, called neighborhood-statistics thinning (NST), to extract the centerline of CNF. Compared with traditional thinning and skeletonization techniques, NST exhibits a better capability to preserve the fine structure of CNF which can effectively benefit the biomarkers measurement above. Moreover, NST incorporates a fitting process, which can make centerline extraction be less influenced by image segmentation. Main results. This new method is evaluated on three datasets which are segmented with five different deep learning networks. The results show that NST is superior to thinning and skeletonization on all the CNF-segmented datasets with a precision rate above 0.82. Last, NST is attempted to be applied for the diagnosis of keratitis with the quantitative biomarkers measured from the extracted centerlines. Longer length and higher density but lower tortuosity were found on the CNF of keratitis patients as compared to healthy patients. Significance. This demonstrates that NST has a good potential to aid in the diagnostics of eye diseases in clinic. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of trigeminal neuralgia (TN) is challenging due to the lack of objective diagnostics. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique, which allows quantification of corneal nerve fibers arising from the trigeminal ganglion and may allow the assessment of neurodegeneration in TN.Methods: CCM was undertaken in 11 patients with TN and 11 age-matched healthy controls. Corneal nerve fiber density (CNFD), corneal nerve branch density, corneal nerve fiber length (CNFL), corneal nerve fiber width, corneal nerve fiber area, and dendritic cell and non-dendritic cell density with or without nerve fiber contact were quantified.Results: Patients with TN had significantly lower CNFD and CNFL but no difference for any other corneal nerve or dendritic cell parameter in the ipsilateral and the contralateral cornea compared to the control group. There was no significant difference in corneal nerve and cell parameters between patients with TN with and without involvement of the ophthalmic nerve (V1) or with nerve vessel conflict.Conclusion: Corneal confocal microscopy is a rapid non-invasive imaging technique that identifies symmetrical corneal nerve loss in patients with TN.

Background: The diagnosis of trigeminal neuralgia (TN) is challenging due to the lack of objective diagnostics. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique, which allows quantification of corneal nerve fibers arising from the trigeminal ganglion and may allow the assessment of neurodegeneration in TN. Methods: CCM was undertaken in 11 patients with TN and 11 age-matched healthy controls. Corneal nerve fiber density (CNFD), corneal nerve branch density, corneal nerve fiber length (CNFL), corneal nerve fiber width, corneal nerve fiber area, and dendritic cell and non-dendritic cell density with or without nerve fiber contact were quantified. Results: Patients with TN had significantly lower CNFD and CNFL but no difference for any other corneal nerve or dendritic cell parameter in the ipsilateral and the contralateral cornea compared to the control group. There was no significant difference in corneal nerve and cell parameters between patients with TN with and without involvement of the ophthalmic nerve (V1) or with nerve vessel conflict. Conclusion: Corneal confocal microscopy is a rapid non-invasive imaging technique that identifies symmetrical corneal nerve loss in patients with TN. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between the duration of type 2 diabetes mellitus (DM) and the ocular surface, and to address the question of why some people with lengthy DM duration are asymptomatic, whereas some people with shorter DM duration have pain or discomfort in their eyes.Methods: Eighty-seven eyes of 87 subjects with different durations of DM and 49 eyes of 49 subjects without DM underwent Schirmer I test, tear film break-up time, sodium fluorescein staining and tear meniscus height (TMH) measurement, and completed the Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire. Corneal structure and function were assessed with in vivo confocal corneal microscopy and with a corneal sensitivity esthesiometer. Both corneal nerve fiber length and inferior whorl length (IWL) were assessed as indices for neural structure. Age and gender were matched between groups. HbA1c levels >7.8% and proliferative diabetic retinopathy were exclusion criteria.Results: In the DM group, compared with the non-DM group, the SPEED score was significantly higher (p = 0.013), and corneal sensitivity and IWL were lower (p < 0.001). Schirmer I test, corneal sensitivity and IWL differed significantly between the group with DM duration >10 years and the non-DM (control) group (p = 0.021, p < 0.001, p < 0.001, respectively). Schirmer I test and IWL were significantly lower in the group with DM >10 years than in the group with DM ≤10 years (p = 0.023, p < 0.001, respectively). Corneal sensitivity was positively correlated with IWL regardless of diabetes status.Conclusions: The lower SPEED score and asymptomatic feeling in people with a longer DM duration may be explained by the decreased IWL and reduced sensitivity. [ABSTRACT FROM AUTHOR]

Aims: To examine and compare fully-automated and manually measured corneal nerve fiber parameters in type 2 diabetes mellitus (T2DM) patients with and without diabetic peripheral neuropathy (DPN).Methods: A total of 128 T2DM subjects and 24 healthy controls underwent neuropathy assessment and bilateral corneal confocal microscopy (CCM). Five representative nerve fiber images were selected for each participant and analyzed manually and with fully-automated software. Corneal nerve fiber length (CNFL), branch density (CNBD), and fiber density (CNFD) were examined.Results: Manual and full-automated methods for the whole cohort were significantly positive correlated for CNFL, CNBD and CNFD (r = 0.818, 0.845, 0.457, all P < 0.001). Analysis of agreement between the two measurements using Bland-Altman method showed a bias of 2.05 mm/mm2 (95% limits of agreement: -2.03 mm/mm2, 6.13 mm/mm2), 1.62 no./mm2 (95% limits of agreement: -17.92 no./mm2, 21.17 no./mm2), and 16.0 no./mm2 (95% limits of agreement: -0.14 no./mm2, 32.14 no./mm2) for CNFL, CNBD and CNFD respectively. A progressive decrease in manual and full-automated CNFL, CNBD and CNFD accompanied with the occurrence of DPN, The fully-automated method slightly underestimated corneal nerve fiber parameters.Conclusions: This study demonstrated strong correlations between manual and fully-automated CNFL and CNBD, but not CNFD. Fully-automated corneal nerve fiber parameter quantification may be a fast, objective way to detect DPN. [ABSTRACT FROM AUTHOR]

Aims: Patients with chronic kidney disease (CKD) in type 2 diabetes typically manifest with severe peripheral neuropathy. Corneal confocal microscopy is a novel technique that may serve as a marker of nerve injury in peripheral neuropathy. This study examines the changes that occur in corneal nerve morphology as a result of peripheral neuropathy due to renal dysfunction in people with type 2 diabetes., Methods: Sixty-two participants (mean age, 62 ± 12 years) with type 2 diabetes and 25 age-matched healthy controls underwent a comprehensive assessment of neuropathy using the total neuropathy score (TNS). The corneal sub-basal nerve plexus was imaged using corneal confocal microscopy. Corneal nerve fiber length, fiber density, branch density, total branch density, nerve fractal dimension, inferior whorl length and inferior whorl nerve fractal dimension were quantified. Based on the eGFR, participants were classified into those with diabetic CKD (eGFR < 60; n = 22) and those without CKD (eGFR ≥ 60; n = 40)., Results: Participants with diabetic CKD had significantly lower corneal nerve fiber density (P = 0.037), length (P = 0.036) and nerve fractal dimension (P = 0.036) compared to those without CKD. Multiple linear regression analysis revealed that reduced corneal nerve fiber density (ß coefficient = 0.098, P = 0.017), length (ß coefficient = 0.006, P = 0.008) and nerve fractal dimension (ß coefficient = 0.001, P = 0.007) was associated with low eGFR levels when adjusted for age, duration of diabetes and severity of neuropathy., Conclusion: Corneal confocal microscopy detects corneal nerve loss in patients with diabetic CKD and reduction in corneal nerve parameters is associated with the decline of kidney function., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)