WASHINGTON — Corneal confocal microscopy provides a means for noninvasively diagnosing neuropathy early on in diabetic patients and for following the course of the disease during treatment, several speakers said at the annual scientific sessions of the American Diabetes Association.
By comparison, the clinical neurologic exam may be easier than corneal confocal microscopy but it lacks sensitivity, said Mitra Tavakoli, a doctoral student at the University of Manchester (England).
Nerve conduction studies are time-consuming and are reliable only in measuring the function of large nerve fibers. Quantitative sensory testing also is easier to do, but relies on the patient's response to take measurements. Skin nerve biopsies can provide much information, but are “highly invasive,” she said.
Using a first-generation corneal confocal microscope, the ConfoScan P4 (Tomey Corp.), Ms. Tavakoli and her colleagues are able to obtain in vivo, real-time micrographs of the cornea at up to 680 times magnification without directly contacting the eye.
She and her coinvestigators studied 183 people including control patients without diabetes, diabetic patients without neuropathy, and diabetic patients with mild, moderate, or severe neuropathy.
They found that diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity (as measured by noncontact corneal aesthesiometry), nerve fiber density, nerve branch density, and nerve fiber length. Nerve fiber tortuosity also became progressively worse as the severity of neuropathy worsened.
The measurements of corneal nerve morphology obtained with confocal microscopy correlated well with assessments of corneal sensitivity and neuropathy severity, as measured by the Neuropathy Disability Score.
In a poster presented at the meeting, Ms. Tavakoli and her colleagues used corneal confocal microscopy to show the effectiveness of pancreatic transplantation in improving neuropathy in 20 patients with type 1 diabetes who had an average age of 41 years.
Before transplantation, the diabetic patients had significantly reduced corneal sensitivity as well as significantly lower nerve fiber density, nerve branch density, and nerve fiber length on corneal confocal micrographs, compared with 18 individuals without neuropathy who had an average age of 55 years.
At 6 months after transplantation, repeat scans in 11 of the patients who had neuropathy showed that nerve fiber density and length had improved significantly. Other posttransplantation studies that have employed electrophysiology and quantitative sensory testing have been able to detect improvements in large fiber function after 3–4 years, unlike the early detection of small fiber repair at 6 months in this study, Ms. Tavakoli reported.
In the laboratory of Nathan Efron, Ph.D.—one of Ms. Tavakoli's collaborators—the microscopy technique has proved to have sensitivity (71%) and specificity (77%) comparable with the histopathologic examination of skin punch biopsy specimens (59% and 90%, respectively) when both are compared with the “gold standard” Neuropathic Disability Score.
Dr. Efron has used confocal microscopy to monitor longitudinal changes in corneal morphology in patients who have received myopic laser in situ keratomileusis (LASIK), which involves cutting a flap of the cornea, irradiating the corneal stroma with a laser, and replacing the flap. The LASIK procedure severs corneal nerves in the subbasal nerve plexus where most of the corneal nerves reside. Several weeks after the surgery, confocal microscopy shows a “hazy image” devoid of any nerve fibers. At 3 months, a few nerve fragments can be seen, and at 6 months a few continuous nerves begin to appear (Optom. Vis. Sci. 2003;80:690–7).
“Certainly, this has implications with respect to diabetic patients who are having this LASIK procedure,” said Dr. Efron, research professor at Queensland University of Technology, Brisbane, Australia.
Confocal micrographs show nerves in a control patient without neuropathy.
By comparison, nerve density is lower in a diabetic patient with neuropathy. Photos courtesy Mitra Tavakoli