Utility Of Corneal Confocal Microscopy To Assessing Diabetic Peripheral Neuropathy In Type 2 Diabetic Patients

Diabetic peripheral neuropathy (DPN) is one of the most common long-term complications of diabetes. Clinical manifestations include pain, paraesthesia and insensitivity, which increase the risk of foot ulceration and lower extremity amputation. Early detection and timely intervention is very important for the treatment of DPN due to the extremely slow process of the nerve fiber regeneration and the lack of effective pharmacological agents. The earliest fibers to undergo damage are small unmyelinated fibers in the progress of DPN. Skin biopsy, a clinical technique used to observe the structure and distribution of small nerve fiber, permit to detect the small nerve fiber damage in patients with impaired glucose tolerance and patients with short duration of DM. However, it is difficult for patients to accept because of the trauma.The corneal is the most densely innervated tissue in the body, which is composed mainly of small unmyelinated fiber. Corneal confocal microscopy (CCM) is a noninvasive technique, it has the capacity to scan the cornea quickly and show the distribution and morphology of corneal nerve plexus in different layers of corneal with high repeatability in vivo. Previous studies showed that, quantification of corneal nerve fiber can accurately reflect the severity of DPN and be a surrogate of skin biopsy to detect the morphology changes of small nerve fiber damage.Recent studies reported that, corneal nerve fiber length was decreased in patients with impaired glucose tolerance, but patients with short duration of DM showed normal nerve fiber length, indicated that early changes of small fiber damage might be repaired in the subsequent progression of DM. The present study aimed to investigate the utility of CCM in detecting early DPN by quantifing morphology changes of corneal nerve fibers in type 2 diabetic patients and identify influence factors of DPN.Subjects and Methods:(1) 61 Patients diagnosed as type 2 diabetes attending diabetes centre or ophthalmology department during the period from MAR-2013 and JUL-2014 were invited to participate in the study.24 healthy volunteers were chosen as the control group. The diabetic patients were stratified into two sub-groups according to the diagnosis of DPN:diabetic peripheral neuropathy (DPN) group and non-diabetic peripheral neuropathy (NDPN) group.(2) General information of individuals was recorded, including age, gender, duration of DM and body mass index (BMI). Type 2 diabetic patients also underwent an assessment of glycosylated haemoglobin (HbAlc), fasting C-peptide (FC-P) and postprandial 2h C-peptide (2h C-P).(3) Individuals underwent CCM examination, high quality images were saved.6 images of each participant were chosen and quantified by software CCMetrics. The following morphological parameters of corneal nerve fiber were recorded:(1) corneal nerve fiber density (NFD); (2) nerve branch density (NBD); (3) nerve fiber length (NFL); (4) nerve fiber tortuosity (NFT). Standardizing corneal nerve fiber length (SDNFL) was calculated by dividing corneal nerve fiber length by nerve fiber tortuosity.(4) NFD, NBD, NFL, NFT, SDNFL and clinical data were compared between each group. Correlations among morphological parameters of corneal nerve fiber and clinical measures were determined.Results:(1) Comparison of basic clinical data:Individuals with DPN had a longer duration of DM and a lower FC-P and 2h C-P level (P<0.05). There was no significant difference in age and BMI between each group.(2) Comparison of morphological parameters:Compared with both control group and NDPN group, diabetic patients in DPN group had reduced NFD, NBD, NFL, SDNFL and increased NFT (P<0.05). Patients in NDPN group showed increased NBD and NFT compared with control group (P<0.05).(3) Analysis of correlation:NBD, NFT and SDNFL showed positive correlation to C-peptide level. NBD and NFT were inversely correlated to duration of DM. Only the SDNFL showed a weak negative correlation with age.Conclusion:(1) Type 2 diabetic patients without DPN had increased NBD and NFT, which is the characteristic of early neuropathy, it prompted that CCM could be used to detect early Peripheral neuropathy.(2) Morphological parameters of corneal nerve fiber differed significantly from Patients without DPN to Patients with DPN, suggest that CCM may be a effective technique to diagnose DPN.(3) The severity of corneal nerve damage had negative correlation with pancreatic islet function and positive correlation with duration of DM. Evaluation of sub-basal corneal neural plexus by CCM in Patients with long duration of DM or low C-peptide level might be helpful to detect early morphological alterlations in peripheral nerve fiber.