Patients with multiple sclerosis demonstrate reduced subbasal corneal nerve fibre density

Background: 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. Objective: 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). Methods: 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. Results: 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. Conclusion: Corneal nerve fibre density is a promising new imaging marker for the assessment of disease severity in MS and should be investigated further.

[1]  M. Mühlau,et al.  Retinal inner nuclear layer volume reflects response to immunotherapy in multiple sclerosis. , 2016, Brain : a journal of neurology.

[2]  B. Uitdehaag,et al.  Timing of retinal neuronal and axonal loss in MS: a longitudinal OCT study , 2016, Journal of Neurology.

[3]  Alexander Klistorner,et al.  Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study , 2016, The Lancet Neurology.

[4]  Pedram Hamrah,et al.  Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy. , 2015, Investigative ophthalmology & visual science.

[5]  L. Kovács,et al.  Dry Eye and Corneal Langerhans Cells in Systemic Lupus Erythematosus , 2015, Journal of ophthalmology.

[6]  I. Zubizarreta,et al.  Dynamics of retinal injury after acute optic neuritis , 2015, Annals of neurology.

[7]  David H. Miller,et al.  Vision and vision-related outcome measures in multiple sclerosis , 2014, Brain : a journal of neurology.

[8]  Blair H. Smith,et al.  Neuropathic pain in the general population: A systematic review of epidemiological studies , 2014, PAIN®.

[9]  F. Paul,et al.  Optic neuritis interferes with optical coherence tomography and magnetic resonance imaging correlations , 2013, Multiple sclerosis.

[10]  G. Kundt,et al.  Imaging and Quantification of Subbasal Nerve Plexus in Healthy Volunteers and Diabetic Patients with or without Retinopathy , 2013, PloS one.

[11]  R. Dana,et al.  Unilateral herpes zoster ophthalmicus results in bilateral corneal nerve alteration: an in vivo confocal microscopy study. , 2013, Ophthalmology.

[12]  C. Crainiceanu,et al.  Microcystic macular oedema, thickness of the inner nuclear layer of the retina, and disease characteristics in multiple sclerosis: a retrospective study , 2012, The Lancet Neurology.

[13]  F. Paul,et al.  Retinal Damage in Multiple Sclerosis Disease Subtypes Measured by High-Resolution Optical Coherence Tomography , 2012, Multiple sclerosis international.

[14]  P. Hamrah,et al.  In Vivo Confocal Microscopy of Immune Cells in the Cornea of Normal Subjects Demonstrates Irregular Peripheral Distribution of Dendritic Cells , 2012 .

[15]  M. Doğru,et al.  Morphological changes of corneal subepithelial nerve plexus in different types of herpetic keratitis , 2011, Japanese Journal of Ophthalmology.

[16]  Pedram Hamrah,et al.  Inflammation and the nervous system: the connection in the cornea in patients with infectious keratitis. , 2011, Investigative ophthalmology & visual science.

[17]  Jeffrey A. Cohen,et al.  Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria , 2011, Annals of neurology.

[18]  Pedram Hamrah,et al.  Corneal sensation and subbasal nerve alterations in patients with herpes simplex keratitis: an in vivo confocal microscopy study. , 2010, Ophthalmology.

[19]  Frauke Zipp,et al.  Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis , 2009, Annals of neurology.

[20]  David H. Miller,et al.  Imaging outcomes for neuroprotection and repair in multiple sclerosis trials , 2009, Nature Reviews Neurology.

[21]  H. Diener,et al.  Prevalence of migraine, tension‐type headache and trigeminal neuralgia in multiple sclerosis , 2009, European journal of neurology.

[22]  M. Mori,et al.  Peripheral nerve demyelination in multiple sclerosis , 2008, Clinical Neurophysiology.

[23]  D. Patel,et al.  In vivo laser scanning confocal microscopy confirms that the human corneal sub-basal nerve plexus is a highly dynamic structure. , 2008, Investigative ophthalmology & visual science.

[24]  B. Vollmar,et al.  In Vivo Confocal Microscopic Evaluation of Langerhans Cell Density and Distribution in the Corneal Epithelium of Healthy Volunteers and Contact Lens Wearers , 2007, Cornea.

[25]  Jeffrey Field,et al.  Schwann cells: origins and role in axonal maintenance and regeneration. , 2006, The international journal of biochemistry & cell biology.

[26]  B. Vollmar,et al.  In vivo confocal microscopic evaluation of Langerhans cell density and distribution in the normal human corneal epithelium , 2005, Graefe's Archive for Clinical and Experimental Ophthalmology.

[27]  B. Weinshenker,et al.  Contrasting effects of IFNβ and IVIG in children with central and peripheral demyelination , 2003, Neurology.

[28]  C. Poser,et al.  Diagnostic criteria for multiple sclerosis , 2001, Clinical Neurology and Neurosurgery.

[29]  Stephen M. Rao,et al.  Development of a multiple sclerosis functional composite as a clinical trial outcome measure. , 1999, Brain : a journal of neurology.

[30]  M. Morimatsu,et al.  [Trigeminal neuralgia in multiple sclerosis]. , 1997, No to shinkei = Brain and nerve.

[31]  P. Profice,et al.  Multiple sclerosis associated with peripheral demyelinating neuropathy. , 1996, Clinical neuropathology.

[32]  J. Niederkorn,et al.  Phagocytosis of particulate antigens by corneal epithelial cells stimulates interleukin-1 secretion and migration of Langerhans cells into the central cornea. , 1989, Regional immunology.

[33]  N. Tachi,et al.  A case of childhood multiple sclerosis with peripheral neuropathy. , 1985, Neuropediatrics.

[34]  A Boyde,et al.  Tandem‐Scanning (Confocal) Microscopy of the Full‐Thickness Cornea , 1985, Cornea.

[35]  L. Missotten,et al.  Lymphocytes and Langerhans cells in the normal human cornea. , 1985, Investigative ophthalmology & visual science.

[36]  W. L. Benedict,et al.  Multiple Sclerosis , 2007, Journal - Michigan State Medical Society.