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

ABSTRACT: Immune 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.

SUBMITTER: Chiang JCB

PROVIDER: S-EPMC8613280 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Characterization of the Corneal Subbasal Nerve Plexus in Limbal Stem Cell Deficiency.

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A Cross-Sectional Study of Sub-Basal Corneal Nerve Reduction Following Neurotoxic Chemotherapy.

Project description:PurposeSub-basal corneal nerves have been shown to change during neurotoxic chemotherapy treatment. This cross-sectional study investigated corneal nerve morphology in patients who have completed neurotoxic chemotherapy well after treatment cessation and its association with peripheral nerve function.MethodsCentral corneal nerve fiber length (CNFL) and inferior whorl length (IWL), average nerve fiber length (ANFL), corneal nerve fiber density (CNFD) and corneal nerve branch density (CNBD), and nerve fiber area (CNFA) were examined using in vivo corneal confocal microscopy in patients with cancer who had completed treatment with either paclitaxel or oxaliplatin between 3 and 24 months prior to assessment in comparison with 2 separate groups of healthy controls. Neurological assessments were conducted including clinician- and patient-reported outcomes, and neurological grading scales.ResultsBoth paclitaxel- (n = 40) and oxaliplatin-treated (n = 30) groups had reduced IWL and ANFL compared to the respective healthy control groups (n = 15 in each group) (paclitaxel: IWL = P = 0.02, ANFL = P = 0.009; and oxaliplatin: IWL = P = 0.008, ANFL P = 0.02). CNFL and CNFD reduction were observed only in the paclitaxel-treated group compared with healthy controls (P = 0.008 and P = 0.02, respectively), whereas CNFA was reduced in the oxaliplatin-treated group (P = 0.04). IWL reduction correlated with worse fine hand dexterity in chemotherapy-treated patients (r = -0.33, P = 0.007).ConclusionsThere is evidence of corneal nerve loss in patients with cancer who have been treated with paclitaxel and oxaliplatin well after treatment cessation associated with worse upper limb function.Translational relevanceSub-basal corneal nerve reduction is evident even after cessation of neurotoxic treatment. In vivo corneal confocal microscopy may be useful in the monitoring of nerve function in patients receiving chemotherapy.

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Analysis of corneal nerve plexus in corneal confocal microscopy images.

Project description: Not available

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Corneal Subbasal Nerve Plexus Changes in Severe Diabetic Charcot Foot Deformity: A Pilot Study in Search for a DNOAP Biomarker.

Project description:Introduction:Diabetic neuroosteoarthropathy (DNOAP) early symptoms are unspecific, mimicking general infectious symptoms and rendering a diagnosis challenging. Consequently, unfavourable outcomes occur frequently, with recurrent foot ulceration, infectious complications, and eventually amputation. Corneal confocal microscopy (CCM) of the subbasal nerve plexus (SNP) is used to detect early peripheral neuropathy in diabetic patients without diabetic retinopathy. This pilot study was designed to determine if specific SNP changes manifest in severe DNOAP in comparison to a healthy control group. Methods:This pilot study utilized a matched-pair analysis to investigate SNP changes by in vivo CCM for 26 patients (mean patient age 63.7 years, range 27 to 78) with severe DNOAP defined by condition after the need for reconstructive foot surgery (n = 13) and a healthy control group (n = 13). Corneal nerve fibre length (CNFL), nerve fibre density (CNFD), nerve branch density (CNBD), average weighted corneal nerve fibre thickness (CNFTh), nerve connecting points (CNCP), and average weighted corneal nerve fibre tortuosity (CNFTo) were assessed as well as the general clinical status, diabetic status, and ophthalmologic basic criteria. Results:In vivo CCM revealed significantly reduced SNP parameters in the DNOAP group for CNFL (p = 0.010), CNFD (p = 0.037), CNBD (p = 0.049), and CNCP (p = 0.012) when compared to the healthy control group. Six patients (46%) of the DNOAP group suffered from diabetic retinopathy and none of the control group. Conclusions:This pilot study revealed a rarefication of SNP in all measured parameters in patients with severe DNOAP. We see a potential value of CCM providing a SNP-based biomarker for early stages of DNOAP prior to the development of any foot deformities that needs to be evaluated in further studies. This trial is registered with German Clinical Trials Register (DKRS) DRKS00007537.

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Patients with multiple sclerosis demonstrate reduced subbasal corneal nerve fibre density.

Project description:Many studies in multiple sclerosis (MS) have investigated the retina. Little, however, is known about the effect of MS on the cornea, which is innervated by the trigeminal nerve. It is the site of neural-immune interaction with local dendritic cells reacting in response to environmental stimuli.This study aims to investigate the effect of MS on corneal nerve fibres and dendritic cells in the subbasal nerve plexus using in vivo confocal microscopy (IVCM).We measured the corneal nerve fibre and dendritic cell density in 26 MS patients and matched healthy controls using a Heidelberg Retina Tomograph with cornea module. Disease severity was assessed with the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale, visual acuity and retinal optical coherence tomography.We observed significant reduction in total corneal nerve fibre density in MS patients compared to controls. Dendritic cell density was similar in both groups. Reduced total nerve fibre density was associated with worse clinical severity but not with previous clinical trigeminal symptoms, retinal neuro-axonal damage, visual acuity or disease duration.Corneal nerve fibre density is a promising new imaging marker for the assessment of disease severity in MS and should be investigated further.

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