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

Overview

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.

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.