Relationship between corneal confocal microscopy and markers of peripheral nerve structure and function in Type 2 diabetes

Abstract

Aims To investigate changes in corneal nerve morphology in Type 2 diabetes and to establish relationships between in vivo corneal confocal microscopy and markers of peripheral nerve structure and function.Participants and methods We recruited 57 participants with Type 2 diabetes and 26 healthy controls of similar age and sex distribution. We also recruited a disease control group of 54 participants with Type 1 diabetes. All participants were assessed for distal symmetrical polyneuropathy using the Total Neuropathy Score. In vivo corneal confocal microscopy was used to assess corneal nerve fibre length, corneal nerve fibre density, corneal nerve branch density and inferior whorl length. Peripheral nerve structure was assessed using median nerve ultrasonography. Large fibre function was assessed according to median nerve axonal excitability. Small fibre function was assessed using Sudoscan TM and the Survey of Autonomic Symptoms.Results Corneal nerve fibre length, fibre density and branch density and inferior whorl length were significantly lower in individuals with Type 2 diabetes compared to controls (P<0.001 for all). In the Type 2 diabetes cohort, correlations were observed between neuropathy severity and corneal nerve fibre density (P=0.004), corneal nerve branch density (P=0.003), corneal nerve fibre length (P=0.002) and inferior whorl length (P=0.01). Significant correlations were observed between corneal confocal outcomes and axonal excitability measurements. No association was found between corneal confocal microscopy and median nerve cross-sectional area, Sudoscan measurements or the Survey of Autonomic Symptoms.Conclusions This study demonstrated significant changes in corneal nerves in individuals with Type 2 diabetes. Reductions in corneal nerve measures correlated with increasing neuropathy severity. Associations were found between corneal confocal microscopy and markers of voltage-gated potassium channel function.

Corneal nerve loss in children with type 1 diabetes mellitus without retinopathy or microalbuminuria

“…AST was lower in the present cohort with type 1 diabetes, and correlated with CNFD, CNBD and CNFL. No relationship between AST and CCM has been observed in studies in adults with diabetes 21,22,30,48 . Although the association between BMI and elevated AST is well established as a marker for liver injury in obese adults [49][50][51][52] , in the present study, AST was inversely correlated with BMI.…”

The diagnostic usefulness of the combined COMPASS 31 questionnaire and electrochemical skin conductance for diabetic cardiovascular autonomic neuropathy and diabetic polyneuropathy

“…Thus, the use of ESC as a marker of distal autonomic function seems to be supported although a conclusive demonstration of its direct assessment of sudomotor function is lacking. Moreover, correlations between ESC and morphology of small fibers have been reported by some authors using skin biopsy parameters although weaker than expected and denied by others using corneal confocal microscopy measures . Finally, ESC has been advocated as a sensitive outcome in an intervention study with bariatric surgery in subjects with prediabetes and type 2 diabetes, but also the associations between ESC and CARTs were inconsistent at 1‐year follow‐up in 37 subjects with type 1 diabetes and free of complications, and the ESC decline unrelated to clinical variables and standard autonomic measures .…”

“…Moreover, correlations between ESC and morphology of small fibers have been reported by some authors using skin biopsy parameters although weaker than expected 15,19,43 and denied by others using corneal confocal microscopy measures. 44 Finally, ESC has been advocated as a sensitive outcome in an intervention study with bariatric surgery in subjects with prediabetes and type 2 diabetes, 45 but also the associations between ESC and…”

Altered peripheral nerve structure and function in latent autoimmune diabetes in adults

“…The machine (MyLabOne, Esaote, Genoa, Italy) was operated under the “Musculoskeletal” factory preset (acoustic power 100%, line density set at medium, dynamic range set at 14, and persistence set at 1) and other settings such as depth, gain, and focus were kept constant for each examination. The median nerve was chosen due to the high reproducibility of the cross‐sectional area (CSA) measurement that can be obtained . Participants were evaluated while sitting comfortably with their forearm fully supinated and fingers semi‐extended.…”

“…The median nerve was chosen due to the high reproducibility of the cross-sectional area (CSA) measurement that can be obtained. 12,18 Participants were evaluated while sitting comfortably with their forearm fully supinated and fingers semi-extended. The forearm was supported on an armrest to ensure the elbow was flexed at 90 .…”