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0001) in patients (1.47?mm?1?��?1.25 SD) than in healthy subjects (8.76?mm?1?��?2.04 SD). Manual estimate of DNFL was significantly lower (p http://www.selleckchem.com/products/i-bet-762.html (3.33?mm?2?��?1.60 SD) than in healthy subjects (6.94?mm?2?��?2.29 SD). Using global spatial sampling, DNFL value was significantly lower (p http://www.selleckchem.com/products/epacadostat-incb024360.html http://www.selleck.cn/products/lee011.html directions of the space. Biological tissues rarely show this characteristic, having most commonly a preferred orientation. This issue can be faced by the introduction of a stereological probe with isotropic orientation. Global spatial sampling occurs in virtual 3D, meaning that it introduces a virtual plane and a probe that are superimposed on the computer screen. We used this approach to obtain an unbiased estimation of dermal nerve morphometry in healthy subjects and in patients with SFN. The quantification of the innervation in the superficial layers of the dermis has been suggested to increase the diagnostic yield of skin biopsy in patients with symptoms of SFN (Vlckova-Moravcova et al., 2008). Recently, we proposed a novel approach based on the manual measurement of a surrogate parameter for DNFL within the entire subepidermal area of 200??m depth from the dermal�Cepidermal junction. Due to the intrinsic characteristics of dermal nerve fiber orientation in the tissue, this surrogate parameter proved to differentiate between normal innervation in healthy subjects and reduced innervation in patients (Lauria et al., 2011). The comparative analysis performed against a 3D stereological computation confirmed this difference.