In Vivo Confocal Microscopy of the Cornea in Diagnosing Small Fibre Neuropathy: A Cross-Sectional Observational Study

Objectives: The aim of this study was to assess the accuracy of corneal in vivo confocal microscopy (IVCM) in the diagnostic process of small fibre neuropathy (SFN) compared to skin biopsy. Methods: This cross-sectional observational study was performed at the Eye Hospital and Institute of Neurophysiology, University Medical Centre Ljubljana, and included 35 patients with a clinical picture of SFN. All patients underwent a neurological exam that included an SFN questionnaire, standard skin biopsy, and ophthalmological assessment, including corneal IVCM. Results: Skin biopsy confirmed SFN in 14/35 patients (40%). These patients had a significantly shorter corneal nerve fibre length (CNFL) compared to those with negative biopsy (13.67 ± 2.99 mm/mm² vs. 16.27 ± 3.54 mm/mm², p = 0.030), as well as reduced corneal nerve branch density (CNBD) (36.68 ± 14.68 branches/mm² vs. 48.81 ± 17.83 branches/mm², p = 0.042). CNFL reduction below the 5th percentile was proven in 13/35 patients, yielding 64.3% sensitivity (95% CI: 35.1-87.2%) and 80.9% specificity (95% CI: 58.1-94.6%) compared to skin biopsy. In idiopathic SFN, negative IVCM results aligned with negative biopsies in 90% (95% CI: 55.5-99.8%) of cases. Meanwhile, in secondary SFN, positive IVCM results detected evidence of peripheral neurodegeneration in an additional 27.3% (95% CI: 6-61%) with negative skin biopsy. Conclusion: CNFL reduction in corneal IVCM demonstrated significant diagnostic value for SFN. Since skin biopsy findings do not always correspond with IVCM findings, corneal IVCM could be applied as a complementary tool to standard skin biopsy rather than as a replacement. It might be additionally useful for detecting patchy pattern presentations of SFN, excluding neuropathy in idiopathic SFN, and detecting neuropathy in biopsy-negative secondary SFN. In patients with positive IVCM, it could also be used as a primary tool for follow-up monitoring.