Corneal confocal microscopy is a non-invasive surrogate of nerve fibre damage and repair in diabetic patients

Abstract

Purpose: The accurate detection and quantification of
human diabetic neuropathy are important to define at risk
patients, anticipate deterioration, and assess new therapies.
Current methods either lack sensitivity, require expert
assessment (neurophysiology) or are highly invasive
(skin/nerve biopsy). Corneal confocal microscopy is a rapid
(2 min) non-invasive in vivo clinical examination technique
capable of quantifying corneal small nerve fibre morphology.
We stratified 102 diabetic patients aged (58 12
years), duration of diabetes (15 11yrs) in accordance with
severity of somatic neuropathy using the Neuropathy Deficit
Score (NDS) (none (1.3 0.9, n = 33), mild (3.9 0.6,
n = 37), moderate (6.8 0.9, n = 22) and severe
(9.8 0.5, n = 12)) and compared to 18 age-matched control
subjects (55.4 8.2 years). Corneal sensitivity using
non-contact (NCCA) ( p = 0.0001) and contact (Cochet-
Bonnett) (CCA) aesthesiometry ( p = 0.007) decreased significantly with increasing neuropathic severity and correlated
with each other ( p = 0.007). NDS correlated with
reduction in corneal sensitivity (NCCA ( p = 0.0001),
CCA ( p = 0.008)). Corneal nerve fibre density (NFD,
p < 0.0001), nerve fibre length (NFL, p = 0.01), nerve fibre
branch density (NBD) ( p < 0.0001) decreased and nerve
fibre tortuosity (NFT) ( p = 0.008) increased in diabetic
patients compared with control subjects. Furthermore, there
was a significant correlation between NDS and NFD
( p = 0.0001), NBD ( p = 0.004) and NFL ( p = 0.011). Corneal
sensitivity may be used as a simple clinical means to
assess severity of somatic neuropathy. Furthermore, corneal
confocal microscopy is a rapid, non-invasive in vivo clinical
examination technique which accurately defines corneal
nerve damage and repair and acts as a surrogate measure
of somatic neuropathy. It represents a significant advance to
simply and reiteratively quantify severity of neuropathy and
may help expedite assessment of therapeutic efficacy in
clinical trials of human diabetic neuropathy.