Corneal Microscopy Detects Diabetic Autonomic Neuropathy

Miriam E. Tucker

September 30, 2014

Corneal confocal microscopy can detect subclinical and overt diabetic autonomic neuropathy, a new study suggests.

Results from a 52-subject trial were presented September 14 at Neurodiab, the annual meeting of the Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes, by optometrist Mitra Tavakoli, PhD, a research fellow at the Centre for Endocrinology & Diabetes, Institute of Human Development, University of Manchester, United Kingdom.

Dr. Tavakoli told Medscape Medical News that the early diagnosis of diabetic autonomic neuropathy can be difficult and is commonly done using cardiac autonomic-function tests as a surrogate. However, those tests are not widely available, have limited sensitivity and specificity, and can be confounded by concomitant cardiovascular disease and cardiac medication.

In the first detailed study assessing the diagnostic utility of corneal confocal microscopy in diagnosing diabetic autonomic neuropathy, Dr. Tavakoli and colleagues found strong correlations between corneal-nerve parameters and the Composite Autonomic Symptom Scale (COMPASS) questionnaire as well as the Composite Autonomic Scoring Scale (CASS), which includes responses to a variety of autonomic-function tests such as sudomotor assessment, orthostatic blood pressure and heart-rate response to tilt, and the Valsalva maneuver.

"The data demonstrate extremely close relationships between the status of the corneal nerves and the severity of autonomic dysfunction and provide excellent sensitivity and specificity for the diagnosis of diabetic autonomic neuropathy," Dr. Tavakoli told Medscape Medical News.

Commenting on the study, Dinesh Selvarajah, MD, clinical diabetes consultant physician, Sheffield Teaching Hospitals Foundation Trust, United Kingdom, told Medscape Medical News: "Corneal confocal microscopy is a promising new technique that is being assessed as an early marker of neuropathy....It measures small fibers in the cornea, and this study shows it relates to other small-fiber dysfunction in diabetes — namely, autonomic neuropathy."

Good Sensitivity, Specificity

The study included 34 subjects with diabetes (23 type 1, 11 type 2), with an average age of 43 years, of whom 19 had diabetic autonomic neuropathy, defined as a CASS score of greater than 2, and who had a diabetes duration of 26 years, compared with just 12.0 years for those without diabetic autonomic neuropathy (CASS score 2 or less).

Mean HbA1c scores were 9.4% for those with diabetic autonomic neuropathy vs 7.6% for those without this complication. Assessments of the 2 diabetes groups were compared with those of 18 age-matched healthy controls.

Corneal-nerve fiber length was 2.6 mm/mm2 in the diabetes patients with diabetic autonomic neuropathy, compared with 7.08 mm/mm2 for those without diabetic autonomic neuropathy and 9.7 mm/mm2 among the healthy controls.

Corneal-nerve fiber density was 13.5/mm2 in those with diabetic autonomic neuropathy, 35.7/mm2 for the diabetes patients without it, and 48.3/mm2 for the controls. Nerve-branch densities were 6.5, 21.2, and 30.1 per mm2, respectively.

All of the differences were statistically significant (P < .0001 for the comparison between diabetes patients with and without diabetic autonomic neuropathy), Dr. Tavakoli reported.

Overall, corneal-nerve parameters correlated with both COMPASS and CASS scales (P < .0001).

At cutoffs of <4.78 mm/mm2 for corneal-nerve fiber length and <23.26 /mm2 for corneal-nerve fiber density, both were 86% sensitive and 78% specific in detecting diabetic autonomic neuropathy. A cutoff of <9.53 /mm2 for nerve-branch density yielded 100% sensitivity and 56% specificity.

Dr. Selvarajah told Medscape Medical News, "This preliminary study demonstrates that corneal confocal-microscopy–measured changes are accompanied by autonomic dysfunction. It provides a proof of concept for future clinical validation studies.…Long-term prospective studies are being performed, and definitive results are awaited."

Dr. Tavakoli noted, "There is clearly a need to standardize the method of capturing, sampling, and analyzing the images in order to use corneal confocal microscopy in longitudinal prospective or interventional multicenter studies."

Neither Dr. Tavakoli nor Dr. Selvarajah have reported relevant financial relationships.

Neurodiab. September 14, 2014; Sopron, Hungary. Abstract O-25.

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