Corneal Confocal microscopy: a novel non-invasive technique to assess nerve fibre damage and repair in diabetic patients

Abstract

Abstract

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.