Prevalence of Decreased Corneal Sensation in Patients With Chronic Inflammatory Demyelinating Polyneuropathy
Condition: Chronic Inflammatory Demyelinating Polyneuropathy
MeSH terms: Polyneuropathies; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Study type: Observational

Summary: 
      Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a demyelinating chronic
      progressive or relapsing neuropathy believed to be secondary to an autoimmune response
      against peripheral nerve antigens.5 We have observed two patients with CIDP with decreased
      corneal sensation who also suffered neurotrophic corneal ulcers and severe visual loss in the
      affected eyes. We want to explore the relationship of CIDP and corneal sensitivity. Our
      hypothesis is that people with CIDP have decreased corneal sensation compared to those
      without. We plan to perform a prospective study measuring corneal sensation in patients
      (proposed n=10) with CIDP and without to determine (1) if a difference exists in patients
      with CIDP compared to controls and (2) the magnitude of the difference. If a difference is
      detected in corneal sensitivity in patients with CIDP, this awareness amongst physicians and
      patients may help prevent blinding complications.
    

Detailed description: 
      INTRODUCTION The prevalence of CIDP ranges from 0.8 to 8.4 per 100 000.5 This broad range may
      reflect the use of different diagnostic criteria, as recently confirmed by an epidemiologic
      study on UK population. Over 50% of the patients may have temporary severe disability during
      the course of their disease and approximately 10% eventually become persistently disabled or
      die because of the illness.

      CIDP may affect any nerve plexus in the body. However, diagnostic criteria leans towards
      nerve conduction studies in the limbs and denervation in other organ systems might be
      overlooked. Sensory innervation of the cornea is provided by the ophthalmic branch of the
      trigeminal nerve via the anterior ciliary nerves. A relatively small number (50-450) of
      primary sensory neurons from the ipsilateral trigeminal ganglion send their peripheral axons
      to the cornea and branch extensively within the corneal tissue. To maintain corneal
      transparency, all peripheral axons of corneal neurons lose the myelin sheath when they enter
      the corneal stroma. Fibers spread in a radial fashion parallel to the corneal surface.1

      Our proposed study will explore the relationship of decreased corneal sensation, a
      potentially devastating eye condition secondary to CIDP. Decreased corneal sensation may lead
      to neurotrophic keratitis; which describes corneal diseases due to impairment or loss of
      corneal sensation leading to epithelial defects and corneal ulcers. This may be caused by
      many ocular and systemic diseases such as Diabetes or Stroke. Corneal innervation is
      important for the maintenance of corneal structure and function, and provides protective
      mechanisms against factors that might be potentially damaging to the cornea. Innervation also
      plays an important trophic function in corneal repair in relation to disease, trauma or
      surgery. Denervation and decreased corneal sensitivity are associated with impairment of
      epithelial and endothelial cell function, increased epithelial and endothelial permeability,
      decreased cell migration and cell mitosis. In addition, denervated corneas are predisposed to
      epithelial or stromal abnormalities, recurrent erosion, impaired wound healing and
      infection.2

      Although corneal nerves lose their myelin sheath as they enter the stroma, the association of
      a demyelinating disease affecting these nerves cannot be excluded. This may be because
      trigeminal nerves can be affected at different levels (the nucleus in the pons, the Gasserian
      ganglion, the trigeminal ophthalmic branch, the nasociliary nerve, or the long ciliary
      nerve). Also, nerves without central myelin throughout their length can be affected in CIDP.
      For example, CNVIII has peculiar myelin as it has central myelin for the majority of its
      length, except for a short distal segment which has peripheral myelin.6 There is one case
      report correlating findings of hearing loss and vestibular dysfunction for over a 6-year
      period in patients with CIDP.

      OUR STUDY

      We plan a prospective clinical trial to compare prevalence of decreased corneal sensation and
      possible decrease in corneal nerves in patients with CIDP previously diagnosed by clinical
      features and electrophysiologic data as outlined by the American Academy of Neurology10 as
      compared to patients without CIDP. Patients will be categorized according to the severity of
      the disease and duration as per their medical records. Exclusion criteria is aimed at those
      conditions which may reduce corneal sensation such as previous eye trauma, surgery, contact
      lens use, eye drop use, or previous viral infections of the eye. A routine complete eye exam
      will be performed along with additional testing for corneal sensation using a standard
      method. If significant findings are obtained during initial eye exam, subjects will obtain
      in-vivo confocal imaging at a second site to image corneal nerve fibers. Published standards
      for corneal sensitivity as well as corneal nerve fiber density via confocal imaging will be
      used in statistical analysis.

      SIGNIFICANCE OF THIS STUDY

      Experimental evidence indicates that impairment of corneal sensory nerves induces
      pathological changes in the anatomic integrity and function of the cornea, particularly in
      the epithelium. Loss of corneal sensory innervations leads to a decrease in thickness of the
      corneal epithelium, intracellular swelling, loss of microvilli and abnormal production of the
      basal lamina. This may lead to impairment in vitality, metabolism, and mitosis of epithelial
      cells and, consequently, epithelial breakdown. Persistent epithelial defects may lead to
      chronic ulceration and eventually to compromise of all ocular surface components with severe
      visual impairment.

      If an association is found between CIDP and decreased corneal sensation, this study will be
      the first one to demonstrate such an association. An increased awareness among physicians
      about this association may lead to a more careful eye exam in patients with CIDP and
      detection of early changes of ocular disease which may be treated earlier so that serious
      blinding complications can be avoided.

      FUTURE STUDIES

      If a positive association is found between CIDP and decreased corneal sensation, the latter
      may be added as a supportive criteria in grading the severity of CIDP. CIDP has many
      treatment modalities available according to its severity and clinical course. Finding
      decreased corneal sensation in CIDP patients prospectively may lead to a diagnosis of
      increased disease severity and patients may benefit from more aggressive treatments.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with severe CIDP.
      
Keywords: Chronic Inflammatory Demyelinating Polyneuropathy; Neurotrophic corneal ulcer