Correlation of Corneal Nerve Microstructure and Function with Peripheral Neuropathy in Diabetes Mellitus using In Vivo Confocal Microscopy

Abstract

Purpose: : Nerve biopsy with electron microscopy, and ex vivo confocal microscopy of skin punch biopsies allow direct examination of nerve fibre damage and repair in diabetes. However, both are invasive procedures and may induce persistent pain at the biopsy site, cold intolerance and sensory deficits. In vivo confocal microscopy (IVCM) avoids these problems by enabling non-invasive imaging of living human corneal nerves. The aim of the current study was to investigate the relationship between corneal sub-basal nerve plexus density, corneal sensitivity, and peripheral neuropathy.

Methods: : Twenty participants (aged 49±12.3 years), with a history of type 1 diabetes mellitus and 10 control participants (aged 47.5±11.4 years) were recruited. Laser scanning IVCM (Heidelberg Retina Tomograph II, corneal module) was performed in one eye of each participant. Central corneal sensitivity was evaluated by non-contact aesthesiometry. An overall neuropathy score was obtained from a combination of symptomatic neuropathy score, clinical assessment, biothesiometry and nerve conduction test. Statistical analysis was performed using SPSS v19.0.

Results: : Median duration of diabetes mellitus was 23 ±12.8 years. The sub-basal nerve density was significantly lower in the diabetic group (14.19± 4.9 mm/mm²) than in the control group (26.35 ± 9.2 mm/mm²) (p<0.01). The corneal sensitivity in the diabetic group was 1.22±0.6 mBAR compared to 0.27±0.3 mBAR (p<0.01) in the control group. Sub-basal nerve density was significantly correlated with corneal sensitivity (r=0.66, p=0.03). Moderate correlation was observed between total neuropathy score and sub-basal nerve density (r=0.39, p=0.16).

Conclusions: : The correlation of corneal sub-basal nerve density with corneal sensitivity and total neuropathy score confirms that corneal nerve changes mirror peripheral neuropathy in diabetes. This enables assessment of nerve damage without the need for painful and invasive biopsies. These results also suggest a possible role for corneal IVCM as a surrogate in assessment of peripheral diabetic neuropathy and monitoring of novel treatments.

Clinical Trial: : http://www.anzctr.org.au ACTRN12610000058077

Keywords: cornea: clinical science • diabetes • imaging/image analysis: clinical