Corneal Confocal Microscopy to Diagnose Peripheral Neuropathy: A Systematic Review and Meta-Analysis

Peripheral neuropathy (PN) may be diagnosed late or may remain undiagnosed. Studies have shown that measurement of corneal nerve fiber length (CNFL) using corneal confocal microscopy (CCM) may have diagnostic utility in diabetic and other peripheral neuropathies.

The main databases [CENTRAL, Embase (Ovid), and PubMed] were searched for peer-reviewed literature. Gray literature searching was undertaken using the ProQuest Dissertations & Theses database. The updated Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used by two authors independently for screening and data extraction. The primary outcome of CNFL was represented by the standardized mean difference and 95% confidence interval, and differences between healthy controls (HC), patients with sub-clinical (PN-), and clinical (PN+) peripheral neuropathy were assessed. Sensitivity analysis was performed to assess the risk of bias.

We identified n = 52 eligible studies (n = 2995 participants) reporting CNFL across 34 different conditions associated with PN. CNFL was significantly lower in PN+ patients compared to HC (standardized mean difference -1.12, 95% confidence interval -1.32 to -0.33, p < 0.00001), in PN- patients compared to HC (-0.78, -0.99 to -0.57, p < 0.00001), and in PN+ compared to PN- patients (-0.93, -1.53 to -0.33, p = 0.002). The results remained significant following sensitivity analysis to adjust for the risk of potential detection bias. The results remained significant independent of the choice of a random or fixed effects model.

This systematic review and meta-analysis shows that CNFL has utility in the diagnosis of peripheral neuropathies.