scholarly journals Corneal dendritic cells and the subbasal nerve plexus following neurotoxic treatment with oxaliplatin or paclitaxel

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeremy Chung Bo Chiang ◽  
David Goldstein ◽  
Azadeh Tavakoli ◽  
Terry Trinh ◽  
Jacob Klisser ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Confocal Microscopy ◽  
Immune Cell ◽  
Healthy Controls ◽  
Corneal Confocal Microscopy ◽  
Significant Difference ◽  
Corneal Nerve ◽  
Cell Densities

AbstractImmune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm2) compared to healthy controls (Md = 10.1 cells/mm2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p < 0.05). There is evidence of elevation of corneal ImDC in oxaliplatin-treated patients. Further investigation is required to explore this potential link through longitudinal studies and animal or laboratory-based immunohistochemical research.

scholarly journals Combining In Vivo Corneal Confocal Microscopy with Deep Learning-based Analysis Reveals Sensory Nerve Fiber Loss in Acute SIV Infection

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.

scholarly journals Evaluation of Corneal Nerves and Dendritic Cells By in Vivo Confocal Microscopy After Descemet’s Membrane Keratoplasty For Bullous Keratopathy

2022 ◽  
Author(s):  
Takahiko Hayashi ◽  
Atsuyuki Ishida ◽  
Akira Kobayashi ◽  
Takefumi Yamaguchi ◽  
Nobuhisa Mizuki ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Confocal Microscopy ◽  
Bullous Keratopathy ◽  
Dependent Manner ◽  
In Vivo Confocal Microscopy ◽  
Descemet Membrane Endothelial Keratoplasty ◽  
Corneal Nerves ◽  
Corneal Nerve ◽  
Number Of Branches

Abstract This study evaluated changes in corneal nerves and the number of dendritic cells (DCs) in corneal basal epithelium following Descemet membrane endothelial keratoplasty (DMEK) surgery for bullous keratopathy (BK). Twenty-three eyes from 16 consecutive patients that underwent DMEK for BK were included. Eyes of age-matched patients that underwent pre-cataract surgery (12 eyes) were used as controls. In vivo confocal microscopy was performed pre- and postoperatively at 6, 12, and 24 months. Corneal nerve length, corneal nerve trunks, number of branches, and the number of DCs were determined. The total corneal nerve length of 1634.7 ± 1389.1 μm /mm2 before surgery was significantly increased in a time-dependent manner to 4485.8 ± 1403.7 μm /mm2, 6949.5 ± 1477.1 μm /mm2, and 9389.2 ± 2302.2 μm /mm2 at 6, 12, and 24 months after DMEK surgery, respectively. The DC density in BK cornea pre- and postoperatively at 6 months was significantly higher than in the controls, and decreased postoperatively at 12 and 24 months and was significantly lower than that at 6 months postoperatively. Thus, our results suggest that DMEK can repair and normalize the corneal environment.

scholarly journals A novel investigation method for axonal damage in neuromyelitis optica spectrum disorder: In vivo corneal confocal microscopy

2021 ◽  
Vol 7 (1) ◽  
pp. 205521732199806
Author(s):  
Ayşe Altıntaş ◽  
Ayse Yildiz-Tas ◽  
Sezen Yilmaz ◽  
Betul N Bayraktutar ◽  
Melis Cansu Comert ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Nerve Fibre ◽  
Disease Severity ◽  
Neuromyelitis Optica ◽  
Spectrum Disorder ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Rnfl Thickness ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

Background Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disorder that damages optic nerves, brainstem, and spinal cord. In vivo corneal confocal microscopy (IVCM) is a noninvasive technique that provides corneal images with dendritic cells (DCs) and corneal subbasal nerve plexus (SBP), which arises from the trigeminal nerve. Objective We investigated corneal SBP changes in NMOSD and proposed IVCM as a potential new disease severity biomarker for NMOSD. Methods Seventeen age-sex matched NMOSD patients and 19 healthy participants underwent complete neurologic and ophthalmologic examinations. The duration of disease, first symptom, presence of optic neuritis attack, antibody status, Expanded Disability Status Scale(EDSS) score and disease severity score(DSS) were recorded. Retinal nerve fibre layer (RNFL) thickness was measured with optical coherence tomography, and corneal SBP images were taken with IVCM. Results NMOSD patients had significantly reduced corneal nerve fibre lenght-density and corneal nerve branch lenght-density compared with controls, while DC density was increased. NMOSD patients also showed significantly reduced RNFL thickness compared with controls. EDSS,DSS levels were inversely correlated with IVCM parameters. Conclusion We observed significant corneal nerve fibre loss in NMOSD patients in relation to disease severity. IVCM can be a candidate noninvasive imaging method for axonal damage assessment in NMOSD that warrants further investigation.

scholarly journals In vivo Confocal Microscopic Evaluation of Corneal Dendritic Cell Density and Subbasal Nerve Parameters in Dry Eye Patients: A Systematic Review and Meta-analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Jing Xu ◽  
Peng Chen ◽  
Chaoqun Yu ◽  
Yaning Liu ◽  
Shaohua Hu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Dendritic Cell ◽  
Nerve Fiber ◽  
Cell Density ◽  
Dry Eye ◽  
Meta Analysis ◽  
Healthy Controls ◽  
Corneal Nerve ◽  
Mean Differences

Purpose: To conduct a systematic review and meta-analysis of the available research on evaluating changes in corneal dendritic cell density (CDCD) and the main subbasal nerve parameters (SNPs) on the ocular surface and assessing the diagnostic performance of in vivo confocal microscopy in patients with dry eye disease.Methods: A computerized systematic review of literature published in PUBMED, EMBASE, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials until May 8, 2020 was performed. All statistical analyses were conducted in RevMan V.5.3 software. The weighted mean differences (WMDs) and standardized mean differences (SMDs) with 95% confidence intervals (CI) between dry eye patients and healthy subjects were presented as results.Results: A total of 11 studies with 755 participants were recruited, and 931 eyes were included in this meta-analysis. However, not all studies reported both CDCD and SNPs. CDCD in the central cornea was higher (WMD = 51.06, 95% CI = 39.42–62.71), while corneal nerve fiber density (CNFD) and corneal nerve fiber length (CNFL) were lower (WMD = −7.96, 95% CI = −12.12 to −3.81; SMD = −2.30, 95%CI = −3.26 to −1.35) in dry eye patients in comparison with the corresponding values in healthy controls (all p &lt; 0.00001).Conclusion: Taken together, while CNFD and CNFL were lower in dry eye patients, central CDCD showed a significant increase in these patients in comparison with the corresponding values in healthy controls.

scholarly journals In vivo corneal confocal microscopy and optical coherence tomography on eyes of participants with type 2 diabetes mellitus and obese participants without diabetes

2021 ◽  
Author(s):  
Noémi Tóth ◽  
David M. Silver ◽  
Szabolcs Balla ◽  
Miklós Káplár ◽  
Adrienne Csutak
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Optical Coherence Tomography ◽  
Type 2 Diabetes Mellitus ◽  
Confocal Microscopy ◽  
Nerve Fibers ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

Abstract Purposes To examine corneal nerve and retinal nerve characteristics of participants with type 2 diabetes mellitus (T2DM) compared with obese participants without diabetes to discover potential nerve vulnerabilities. Methods All participants underwent a complete medical examination including a physical examination and blood sample tests. The ophthalmologic examination included best-corrected visual acuity, intraocular pressure, Schirmer test, tear film breakup time, slit-lamp examination, dilated fundus photography, in vivo corneal confocal microscopy (IVCCM), and optical coherence tomography (OCT). Results The study cohort consisted of 83 eyes of 83 individuals: a group of 44 participants with T2DM, and a control group of 39 obese participants with no history of diabetes. Comparing measurements on the two groups, participants with T2DM had lower values with statistical significance for retinal nerve fiber layer (RNFL) nasal superior thickness (p = 0.010) and three corneal nerve (CN) parameters: fiber length (p = 0.025), total branch density (p = 0.013), and fiber area (p = 0.009). There was a borderline significant difference in CN fiber width (p = 0.051) and RNFL nasal inferior thickness (p = 0.056). No other significant differences were observed in the IVCCM and OCT parameters. No statistically significant correlation was found between CN and RNFL parameters. Conclusions Progression from a pre-diabetic obese state to a T2DM condition might entail a loss or diminishment of certain corneal nerve fibers or retinal nerve fibers, but not necessarily a loss of both corneal and retinal nerve fibers simultaneously. Using IVCCM and OCT together enables monitoring of both corneal and retinal health of the eye.

scholarly journals Corneal confocal microscopy detects corneal nerve damage and increased dendritic cells in Fabry disease

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Gulfidan Bitirgen ◽  
Kultigin Turkmen ◽  
Rayaz A. Malik ◽  
Ahmet Ozkagnici ◽  
Nazmi Zengin
Keyword(s):  
Dendritic Cells ◽  
Confocal Microscopy ◽  
Fabry Disease ◽  
Nerve Damage ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

In Vivo Confocal Microscopy Demonstrates Increased Immune Cell Densities in Corneal Graft Rejection Correlating With Signs and Symptoms

2019 ◽  
Vol 203 ◽  
pp. 26-36 ◽  
Author(s):  
Chareenun Chirapapaisan ◽  
Alessandro Abbouda ◽  
Arsia Jamali ◽  
Rodrigo T. Müller ◽  
Bernardo M. Cavalcanti ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Graft Rejection ◽  
Immune Cell ◽  
Signs And Symptoms ◽  
Corneal Graft ◽  
In Vivo Confocal Microscopy ◽  
Corneal Graft Rejection ◽  
Cell Densities

scholarly journals In Vivo Corneal Confocal Microscopy Detects Improvement of Corneal Nerve Parameters following Glycemic Control in Patients with Type 2 Diabetes

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaofan Jia ◽  
Xiaogang Wang ◽  
Xiaoxia Wang ◽  
Qi Pan ◽  
Tongzhang Xian ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Confocal Microscopy ◽  
Nerve Conduction ◽  
Corneal Confocal Microscopy ◽  
Group A ◽  
Corneal Nerve ◽  
Group B

Aim. This study aimed to investigate whether in vivo corneal confocal microscopy (CCM) can detect the improvement of corneal nerve parameters following glycemic control in patients with type 2 diabetes in natural history. Methods. Thirty-two patients with diabetes complicated by DPN and 12 age-matched control subjects underwent detailed clinical examination and were assessed per the Toronto Clinical Scoring Scale for DPN, nerve conduction studies, and IVCCM at baseline and after approximately one year from the first visit. Results. At follow-up, 16 diabetic patients had improved glycemic control (group A, HbA1c < 7.0%, 7.78 ± 1.62% versus 6.52 ± 0.59%, P=0.005), while the remainder continued to have elevated HbA1c levels (group B, HbA1c ≥ 7.0%, 8.55 ± 1.57% versus 8.79 ± 1.05%, P=0.527). For patients in group A, corneal nerve fiber density (CNFD) (18.55 ± 5.25 n/mm2 versus 21.78 ± 6.13 n/mm2, P=0.005) and corneal nerve fiber length (CNFL) (11.62 ± 2.89 mm/mm2 versus 13.04 ± 2.44 mm/mm2, P=0.029) increased significantly compared to baseline. For patients in group B, sural sensory nerve conduction velocity (47.93 ± 7.20 m/s versus 44.67 ± 6.43 m/s, P=0.024), CNFD (17.19 ± 5.31 n/mm2 versus 15.67 ± 4.16 n/mm2, P=0.001), corneal nerve branch density (19.33 ± 12.82 n/mm2 versus 14.23 ± 6.56 n/mm2, P=0.033), and CNFL (11.16 ± 2.57 mm/mm2 versus 9.90 ± 1.75 mm/mm2, P=0.011) decreased significantly. Conclusions. The results of this study suggest that morphological repair of corneal nerve fibers can be detected when glycemic control improves. In vivo CCM could be a sensitive method that can be applied in future longitudinal or interventional studies on DPN.

scholarly journals Small fiber neuropathy for assessment of disease severity in amyotrophic lateral sclerosis: corneal confocal microscopy findings

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Jiayu Fu ◽  
Ji He ◽  
Yixuan Zhang ◽  
Ziyuan Liu ◽  
Haikun Wang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Dendritic Cell ◽  
Confocal Microscopy ◽  
Disease Severity ◽  
Peripheral Region ◽  
Small Fiber Neuropathy ◽  
Small Fiber ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve ◽  
Lateral Sclerosis

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with progressive motor system impairment, and recent evidence has identified the extra-motor involvement. Small fiber neuropathy reflecting by sensory and autonomic disturbances in ALS has been reported to accompany the motor damage. However, non-invasive assessment of this impairment and its application in disease evaluation of ALS is scarce. We aim to evaluate the use of corneal confocal microscopy (CCM) to non-invasively quantify the corneal small fiber neuropathy in ALS and explore its clinical value in assessing disease severity of ALS. Methods Sixty-six patients with ALS and 64 healthy controls were included in this cross-sectional study. Participants underwent detailed clinical assessments and corneal imaging with in vivo CCM. Using ImageJ, the following parameters were quantified: corneal nerve length (IWL) and dendritic cell density (IWDC) in the inferior whorl region and corneal nerve fiber length (CNFL), nerve fiber density (CNFD), nerve branch density (CNBD), and dendritic cell density (CDC) in the peripheral region. Disease severity was evaluated using recognized scales. Results Corneal nerve lengths (IWL and CNFL) were lower while dendritic cell densities (IWDC and CDC) were higher in patients with ALS than controls in peripheral and inferior whorl regions (p < 0.05). Additionally, corneal nerve complexity in the peripheral region was greater in patients than controls with higher CNBD (p = 0.040) and lower CNFD (p = 0.011). IWL was significantly associated with disease severity (p < 0.001) and progression (p = 0.002) in patients with ALS. Patients with bulbar involvement showed significantly lower IWL (p = 0.014) and higher IWDC (p = 0.043) than patients without bulbar involvement. Conclusions CCM quantified significant corneal neuropathy in ALS, and alterations in the inferior whorl region were closely associated with disease severity. CCM could serve as a noninvasive, objective imaging tool to detect corneal small fiber neuropathy for clinical evaluation in ALS.

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