Increased Langerhan cell density and corneal nerve damage in diabetic patients: role of immune mechanisms in human diabetic neuropathy

Abstract

Aim/hypothesis: Immune mechanisms have been proposed to play a role in the development of diabetic neuropathy. We employed in vivo corneal confocal microscopy (CCM) to quantify the presence and density of Langerhans cells (LCs) in relation to the extent of corneal nerve damage in Bowman's layer of the cornea in diabetic patients.

Methods: 128 diabetic patients aged 58 ± 1 yrs with a differing severity of neuropathy based on Neuropathy Deficit Score (NDS-4.7 ± 0.28) and 26 control subjects aged 53 ± 3 yrs were examined. Subjects underwent a full neurological evaluation, evaluation of corneal sensation with non-contact corneal aesthesiometry (NCCA) and corneal nerve morphology using corneal confocal microscopy (CCM).

Results: The proportion of individuals with LCs was significantly increased in diabetic patients (73.8%) compared to control subjects (46.1%), P = 0.001. Furthermore, LC density (no/mm(2)) was significantly increased in diabetic patients (17.73 ± 1.45) compared to control subjects (6.94 ± 1.58), P = 0.001 and there was a significant correlation with age (r = 0.162, P = 0.047) and severity of neuropathy (r = -0.202, P = 0.02). There was a progressive decrease in corneal sensation with increasing severity of neuropathy assessed using NDS in the diabetic patients (r = 0.414, P = 0.000). Corneal nerve fibre density (P < 0.001), branch density (P < 0.001) and length (P < 0.001) were significantly decreased whilst tortuosity (P < 0.01) was increased in diabetic patients with increasing severity of diabetic neuropathy.

Conclusion: Utilising in vivo corneal confocal microscopy we have demonstrated increased LCs in diabetic patients particularly in the earlier phases of corneal nerve damage suggestive of an immune mediated contribution to corneal nerve damage in diabetes.

Figure 1

Images from Bowman’s layer of the cornea with highly reflective cells “presumably Langerhans cells”. (a) control subject (b) diabetic patient with mild neuropathy (c) diabetic patient with severe neuropathy.

Figure 2

Density of Langerhans cells (a) in diabetic patients compared to control subjects (P=0.001) (b) in diabetic patients according to severity of neuropathy (control v none P=0.045, v mild P=0.004, v moderate: P=0.393, v severe: P=0.932) (c) comparing patients with type I and type II diabetes. (For each group, horizontal bars illustrate the mean and vertical bars illustrate the SE.)