Corneal Confocal Microscopy and Neuropathy
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin reports no financial relationships relevant to this field of study.
Synopsis: Confocal microscopy of the cornea may be a useful diagnostic test to identify patients with small-fiber neuropathies.
Source: Gemignani F, etal. Non-length-dependent small-fibre neuropathy. Confocal microscopy study of the corneal innervation. J Neurol Neurosurg Psychiatry 2010;81:731-733.
Skin-punch biopsy is an invasive, yet easily performed, well-accepted method for objectively documenting the presence of small-fiber neuropathy, and single-site biopsy is usually sufficient for the diagnosis of distal symmetric small-fiber neuropathy. For non-length-dependent small-fiber neuropathy/ganglionopathy, a variant of small-fiber neuropathy where the distal limb is spared relative to more proximal regions, multiple site biopsies may be warranted. Corneal confocal microscopy, a rapid, noninvasive, clinical examination that quantifies small nerve fiber pathology and allows for investigation of the sensory trigeminal nerve terminals in the cornea, has been shown to be a useful noninvasive surrogate for demonstrating nerve fiber damage and repair in distal symmetric small-fiber neuropathy (Diabetologia 2003;46:683-688). The same appears to be true for the non-length-dependent variant, as well.
Six consecutive patients with non-length-dependent, small-fiber neuropathy underwent in vivo corneal nerve fiber density evaluation using laser corneal confocal microscopy. Criteria for diagnosis included a history of pain or dysesthesiae involving the proximal limbs, face, or trunk, as opposed to the usual stocking-glove pattern, with a similar distribution of small-fiber sensory abnormalities on examination, including thermal testing with metal thermorollers, and decreased intra-epidermal nerve fiber density on 3-mm skin punch biopsy. Large-fiber neuropathy was excluded using conventional nerve conduction studies, and evidence of such on examination was reason for exclusion. Causes of small-fiber neuropathy included Sjögren's syndrome, impaired glucose tolerance, and hepatitis C virus infection with Crohn's disease in one patient each, with three patients carrying a diagnosis of idiopathic neuropathy. In all patients, corneal confocal microscopy demonstrated decreased corneal nerve fiber density and poor branching in Bowman's layer, the acellular transparent sheet of fine collagen fibrils lying beneath the outer layer of stratified epithelium of the cornea. Corneal confocal microscopy, although requiring special expertise and not widely available, appears to be a useful, noninvasive alternative to skin-punch biopsy in documenting small fiber neuropathy. Additional studies should be performed in larger populations to confirm the usefulness of this test in the diagnosis of small-fiber neuropathy.
Commentary
Despite extensive evaluation, the etiology of most small-fiber neuropathies remain undiagnosed. Characterized by burning feet; sharp, lancinating pain; and numbness or paresthesiae in the feet, examination usually reveals reduced pain and temperature sensation in a stocking distribution with intact large-fiber function, including Achilles deep tendon reflexes. Causes include ethanol abuse (perhaps the most common cause in the United States), diabetes, amyloid, Sjögren's syndrome, vasculitis, human immunodeficiency virus (HIV) infection, and drugs or toxins. Measurement of the erythrocyte sedimentation rate, fasting blood glucose, glycosylated hemoglobin, serum and urinary protein electrophoresis and immunoelectrophoresis, antinuclear antibodies, Sjögren antibodies (anti-Ro and anti-La or SSA and SSB) and the oral glucose-tolerance test may be cost effective, but anti-GM1, anti-MAG, or antisulfatide antibody measurements are rarely helpful. Treatment consists of addressing the underlying cause, but for the idiopathic majority, symptomatic pain relief is often the only option. Tricyclic antidepressants, antiepileptic agents, topical local anesthetics, and opioids are helpful.
Confocal microscopy of the cornea may be a useful diagnostic test to identify patients with small-fiber neuropathies.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content