New Eye Scan Predicts Peripheral Neuropathy in Diabetes

Miriam E Tucker

January 22, 2015

Corneal confocal microscopy (CCM) predicts incipient peripheral neuropathy in patients with type 1 diabetes, a new study finds.

The technique involves the examination of unmyelinated nerve fibers at high magnification using a laser-scanning corneal confocal microscope to image the subbasal nerve plexus of the patient's cornea. Increased severity of diabetic peripheral neuropathy is associated with reduced corneal-nerve fiber length and corneal sensitivity.

The results were published online January 8, 2015 in Diabetes Care by Nicola Pritchard, of Queensland University of Technology, Australia, and colleagues.

Previous studies have demonstrated utility for CCM in assessing peripheral diabetic neuropathy, autonomic neuropathy, and neuropathy in those with prediabetes.

In the current study of 90 initially nonneuropathic patients with type 1 diabetes, CCM had 63% sensitivity and 74% specificity for detecting 4-year incidence of diabetic peripheral neuropathy using a corneal-nerve fiber-length cutoff of 14.1 mm/mm2.

"This is a hugely important study, as it shows for the first time that CCM can be used to predict those who will develop diabetic peripheral neuropathy," study coauthor Dr Rayaz A Malik (Weill Cornell Medical College, New York and Qatar) told Medscape Medical News.

"In an ideal world, we would see this as a screening tool much like diabetic retinal screening for retinopathy and microalbuminuria for incipient nephropathy. This is based on data showing that CCM abnormality is present very early and occurs even in patients without retinopathy or microalbuminuria," Dr Malik explained.

Asked to comment, Dr Tunde Peto (Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom) told Medscape Medical News: "Corneal-nerve fiber-length measurement would be a good addition to current diagnostic tools….[It is] noninvasive and objective and, compared with all other measurements, is fast and reproducible. The imaging does not depend on the patient's ability to say whether they can feel hot/cold/vibration and also does not depend on experienced technicians doing nerve-conduction studies."

However, Dr Peto, who was not involved in this new study, also pointed out, "The current drawback is that not many units have the imaging tool and even fewer have the software to actually carry out the measurements reliably."

Moreover, "It will require a shift in the thinking process of looking at the eye and not the feet for this, and so there will be a need for large-scale thorough studies to enable clinicians and patient groups to be sure that no relevant clinical disease is missed once the technique is rolled out to the wider community of patients with diabetes," he added.

Predicting Neuropathy

The new study enrolled 101 patients aged 14 to 80 years who had no peripheral neuropathy at baseline. Of the 90 who were assessed at 4 years, 16 (18%) had developed diabetic peripheral neuropathy.

An adaptation of the "Toronto criteria" was used to diagnose diabetic peripheral neuropathy, including abnormal nerve-conduction velocity (relative to normal for age)and a symptom or sign of neuropathy, which was defined as one or more of the following: a diabetic neuropathy symptom score of 1 or more out of 4 or a neuropathy disability score of 3 or more of 10.

Considered the "gold standard," the 2010 Toronto criteria have been endorsed by leading experts in the field of diabetic neuropathy worldwide.

However, Dr Malik explained, "It is really used only in clinical studies. In the real world, ie, clinical practice, there is huge variation, and most clinicians will still use the monofilament or clinical exam, which we know picks up only advanced neuropathy and is highly variable."

With CCM, results showed that corneal-nerve fiber length was significantly lower among those who had developed diabetic peripheral neuropathy at 4 years, 14.0 mm/mm2, compared with 16.2 mm/mm2 among those who did not (P = .041).

Other significant predictors included: longer duration of diabetes; higher triglycerides; retinopathy; nephropathy (higher albumin-to-creatinine ratio; P = 0.001); higher neuropathy disability score; lower cold-sensation and cold-pain thresholds; higher warm-sensation and warm-pain and vibration thresholds; impaired monofilament response; and slower peroneal and sural-nerve-conduction velocities.

Cold-sensation threshold had the highest predictive capacity, with sensitivity 88% and specificity 55% at a cutoff of 29.2°C.

Only two assessments, corneal-sensation threshold and the neuropathy-symptom score, did not significantly predict diabetic peripheral neuropathy.

"These findings confirm an expanded role of CCM in the assessment of diabetic peripheral neuropathy as a supplement to the wide array of neurological tests currently in use," the authors state.

What Role Could CCM Play?

Dr Peto told Medscape Medical News, "Where possible, [CCM] could be added to the battery of current tests, and as more data are gathered and better understanding is achieved both on advantages and potential disadvantages of this technique, certain other tests might become less frequently used."

She also noted, "As the patients do not have to undress for this measurement, it would fit well with the examination flow, as it could be part of the battery of tests done before the doctor sees the patient, and the results might be available by then should it be possible to automate the measurement."

She did caution, though, that there are potential problems with using CCM in patients who have had ophthalmic operations such as cataract or glaucoma surgery.

Dr Malik said that he and his colleagues are working on an algorithm that would incorporate CCM into a clinical-assessment paradigm for diabetic peripheral neuropathy. For example, it might be considered the first-line test for patients with autonomic symptoms or pain.

He noted that there are currently about 600 CCM units worldwide and another 2000 that could be modified for that purpose. A single unit costs about $50,000, and each test would probably cost around $5. His team also plans to conduct a cost-effectiveness study.

"If used regularly, given the number of patients with diabetes, I would expect [CCM] to be cost-effective, especially given how expensive and time-consuming the other modalities are," Dr Peto said.

"Diabetic peripheral neuropathy is an expensive disease to treat and can be extremely debilitating to the patient. Early, reliable, noninvasive, reproducible, and quick diagnosis might lead to earlier treatment that might slow down or halt the progression of the disease, which would be of great benefit for the community," she concluded.

The study was funded by the National Health and Medical Research Council of Australia and the Juvenile Diabetes Research Foundation. The study authors and Dr Peto have reported no relevant financial relationships.

Diabetes Care. Published online January 8, 2015. Abstract

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