Publications (5)0 Total impact
ABSTRACT: Purpose:There is an urgent need to develop surrogate markers to aid in the diagnosis and assessment of treatment efficacy in human diabetic neuropathy.
Methods: 22 diabetic patients underwent detailed assessment of Neuropathy Impairment Score in the lower limbs (NIS–LL), electrophysiology (EMG), quantitative sensory testing (QST), corneal confocal microscopy (CCFM) and skin biopsy. On the basis of NIS–LL, EMG and QST assessment 11 patients were classed to have no neuropathy, and 11 had neuropathy.
CCFM was performed to quantify corneal nerve morphology: nerve fibre density (NFD), tortuosity (NFT), and branch density (NBD) were compared with normative values from healthy control group.
3 mm punch skin biopsies were performed from the dorsum of the foot and immunohistochemical staining was performed with PGP 9.5 to quantify dermal nerve fibre density (DNFD) and compared with normative values from 23 volunteers (aged sex matched)
Results:1) CCFM demonstrated differences between non neuropathic diabetic, neuropathic diabetic and control groups. Respective results are given as mean ± SD: NFD 29±10, 35±13, and 46±16 nerves/mm2 (P=0.02); NFT 8±8, 19 ±14, 24±10 (tortuosity index, P=0.002), NFBD 6±2, 6±3, 33±26 branches/mm2 (p<0.001).
2) DNFD was reduced in all diabetic patients, non neuropathic and neuropathic, compared to controls (respectively 203±114, 190±58, and 414±196 fibres/mm2 (P<0.001). No differences between the two patient groups were showed by post–hoc analysis.
Conclusions:Whilst both CCFM and DNFD were more reduced in diabetic patients with compared to those without neuropathy this did not reach significance. Corneal nerve morphology and skin DNFD correlated with electrophysiological parameters. However they did not correlate to each other. This preliminary study demonstrates significant associations between corneal nerve morphology, ENFD and conventional measures of neuropathic severity suggesting that they may be reliable surrogate measures of human diabetic neuropathy.
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.
Purpose:The accurate detection and quantification of human diabetic neuropathy are important to define at risk patients, anticipate deterioration, and assess new therapies. Corneal confocal microscopy (CCM) is a in vivo clinical examination technique capable of quantifying corneal small nerve fibre morphology.
Methods:158 diabetic patients with increasing neuropathic severity according to the Neuropathy Deficit Score (NDS) (none (1.29 ± 0.9, n= 52), mild (3.90 ± 0.70, n=50), moderate (7.07 ± 0.91, n= 28) and severe (9.78 ± 0.42, n=28)) and 25 age-matched control subjects (54 ± 16 yrs) were studied.
Results:Corneal sensitivity using non-contact (NCCA)( p=0.0001) and contact (CBA) aesthesiometry (p=0.007) decreased significantly with increasing neuropathic severity and correlated with NDS (NCCA (p<0.0001), CCA (P=0.008)). Corneal nerve fibre density (NFD, p<0.0001), length (NFL, p<0.0001), branch density (NBD) (p<0.0001) decreased and nerve fibre tortuosity (NFT) (p<0.0001) increased in diabetic patients compared with controls. Furthermore, there was a significant correlation between NDS and NFD (p<0.0001), NBD (p=0.004), NFL (p<0.0001) and NFT(p=0.004). We also studied 20 diabetic patients within 1 month of pancreas transplantation (PTx) and 18 control subjects. Diabetic patients undergoing PTx demonstrate a marked reduction in corneal NFD (13.4 8.9 v 51.9 10.3, p =0.0001), NBD (3.7 6.4 v 28.9 14.3, p=0.0001), NFL (2.2 1.2 v 9.1 6.0, P=0.001) and NFT (15.1 3.1 v 24.4 10.5, p=0.08). 6 months after PTx 15 patients underwent repeat assessment and showed a significant improvement in NFD (18.04 5.75 v 9.25 7.26, p= 0.001) with trends for improvement in corneal sensitivity (NCCA), (1.23 1.18 v 1.54 1.19 , p=0.59), no changes in NBD (1.38 3.89 v 1.38 2.87 , p=1 ), increase in NFL (3.60 1.16 v 1.84 1.44 , p=0.002) and reduction in NFT (15.58 3.98 v 16.30 3.76, p=0.67).
Conclusions:Loss of corneal sensation and corneal nerve fibre damage occurs with increasing severity of diabetic neuropathy and despite significant damage at baseline in patients undergoing PTx, small nerve fibres regenerate within 6 months. CCM is a novel non-invasive clinical technique which may be used to quantify the severity of neuropathy and may help expedite assessment of therapeutic efficacy in clinical trials of human diabetic neuropathy.