Prevalence of Decreased Corneal Sensation in Patients With Chronic Inflammatory Demyelinating Polyneuropathy

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.

Inclusion Criteria:

- Participants must be > 18 years of age. Patients with severe CIDP will be enrolled
with age-matched controls without CIDP.

Exclusion Criteria:

- Eye disease (prior or current) other than glasses, Prior eye injury/ trauma, Viral
infection (HSV/VZV - prior or current) of eye, Use of contact lenses in last month,
Prior eye surgery / laser/lasik, and Use of eye drops other than artificial tears.