Corneal confocal microscopy in patients with distal symmetric polyneuropathy compared to controls

Abstract

Background Diabetic neuropathy (DN) is a very common clinical condition throughout the world. The diagnostic tests currently recommended have low sensitivity, such as electromyography, or are invasive, such as skin biopsy. New techniques have been developed to identify the early involvement of the peripheral nerve. With the advent of corneal confocal microscopy (CCM), a reduction in corneal innervation in patients with DN has been observed. Objective To compare, through CCM, diabetic patients with symptomatic distal symmetric polyneuropathy (DSP) and controls. Methods In the present study, through CCM, we compared the morphological changes in the sub-basal epithelial corneal plexus of 35 diabetic patients with symptomatic DSP with 55 controls. Moreover, we sought to determine a pattern of change regarding the severity stages of DSP, comparing the clinical, laboratory, and nerve-conduction (NC) variables. Results Differences between the control and diabetic groups were observed for the following variables, respectively: age (44.9 ± 13.24 years versus 57.02 ± 10.4 years; p < 0.001); fiber density (29.7 ± 10.2 versus 16.6 ± 10.2; p < 0.001); number of fibers (4.76 ± 1.30 versus 3.14 ± 1.63; p < 0.001); number of Langerhans cells (4.64 ± 8.05 versus 7.49 ± 10.3; p = 0.035); tortuosity (p < 0.05); and thickness (p < 0.05). Furthermore, inverse relationships were found regarding fiber density and age (p < 0.01) and fiber density and the severity of the disease (p < 0.05). A positive relationship between the conduction velocity of the fibular nerve and fiber density (p < 0.05) was also observed. Conclusion Corneal confocal microscopy proved to be a fast, noninvasive and reproducible method for the diagnosis, staging, and monitoring of diabetic DSP.

Corneal confocal microscopy for the assessment of diabetic neuropathy and beyond in Brazil

“… 4 In a large multi-center study funded by the National Institutes of Health (NIH), we confirmed that CCM has excellent diagnostic utility 5 and also predicts the development of clinical diabetic neuropathy. 6 Consistent with the study by Pupe et al, 1 early subclinical corneal nerve loss has been shown in children with type-1 diabetes, 7 and subjects with impaired glucose tolerance 8 and recently-diagnosed type-2 diabetes. 9 Normative values for corneal nerves have been established, and they show a small age-dependent decrease but no impact of height, weight, or body mass index (BMI).…”

“…In conclusion, the study by Pupe et al 1 reinforces the results of many other studies showing that CCM is a robust end point for the assessment of neurodegeneration in diabetic neuropathy and other peripheral neuropathies, as well as central neurodegenerative diseases. Brazil is home to an epidemic of diabetes and diabetic neuropathy, as well as many other neuropathies, such as leprosy, B 12 deficiency, HIV, amyloidosis and, of course, long COVID.…”

“…9 Normative values for corneal nerves have been established, and they show a small age-dependent decrease but no impact of height, weight, or body mass index (BMI). 10 This is reassuring, as the study by Pupe et al 1 showed corneal nerve loss in patients with diabetic neuropathy, despite the controls being significantly older. In our recent study 11 of 490 participants with diabetes, corneal nerve loss was associated with low-density lipoprotein (LDL) cholesterol and triglycerides values in type-1 diabetes, and with age, weight and hemoglobin A1c (HbA1c) in type-2 diabetes.…”

“…The study by Pupe et al 1 is the first paper from Brazil and indeed South America showing that corneal confocal microscopy (CCM) can identify small nerve fiber damage and increased Langerhans cells in patients with diabetic neuropathy. Despite the inclusion of only 35 patients with diabetes and overall good glycemic control, corneal nerve loss was evident in patients with ‘mild neuropathy’ based on symptoms and nerve conduction, which progressively worsened with increasing severity of the diabetic neuropathy.…”