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The laser Doppler imaging (LDI)  FLARE  and corneal confocal microscopy (CCM) are reliable markers of small fibre function (SFF) and structure (SFS), respectively, but the impact of potential confounding variables needs to be defined. The objective of this study was to determine the influence of age, anthropometric and biochemical variables on LDI and CCM.    Methods  80 healthy volunteers (43 males) (age: 39.7±15.2 yrs.) underwent LDI FLARE  and CCM assessment and the effect of age, anthropometric and biochemical variables was determined using multivariate analysis.    Results  There was an age-related decline in LDI FLARE  (0.07cm 2 /yr; R 2  = 0.669; p = <0.0001) and CCM parameters (CNFD: 0.05 fibres/mm 2  /yr; R 2  = 0.590; p = <0.0001, CNBD: 0.06 branches/mm 2 /yr; R 2  = 0.549; p = 0.001and CNFL 0.07 mm/mm 2 /yr; R 2  = 0.369; p = 0.009). BMI did not influence SFF (p = 0.08) but had a significant independent association with CNFD (p = 0.01). Fasting triglycerides (TG) independently influenced the LDI FLARE  (β c :-0.204; p = 0.008) and all CCM indices (β c :-0.191 to -0.243; p = <0.05). HbA 1c  was significantly associated with CNFD only (p = 0.001) but not with LDI FLARE , CNBD or CNFL (p = ≥0.05). Blood pressure and total cholesterol were not associated with LDI FLARE  or any CCM parameters. There was a significant correlation between LDI FLARE  and all CCM parameters (p = ≤0.01).    Conclusions  This study shows that in healthy controls, both SFF measured by LDI FLARE  and SFS assessed by CCM showed a significant inverse correlation with age and triglycerides, perhaps suggesting the use of age-specific normative values when interpreting these outcomes. Furthermore, this study shows that in healthy controls, despite measuring different neural parameters, both methods correlated significantly with each other.

The influence of age, anthropometric and metabolic variables on LDIFLARE and corneal confocal microscopy in healthy individuals