The Utility of Corneal Nerve Fractal Dimension Analysis in Peripheral Neuropathies of Different Etiology

PURPOSE: Quantification of corneal confocal microscopy (CCM) images has shown a significant reduction in corneal nerve fiber length (CNFL) in a range of peripheral neuropathies. We assessed whether corneal nerve fractal dimension (CNFrD) analysis, a novel metric to quantify the topological complexity of corneal subbasal nerves, can differentiate peripheral neuropathies of different etiology. METHODS: Ninety patients with peripheral neuropathy, including 29 with diabetic peripheral neuropathy (DPN), 34 with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 with chemotherapy-induced peripheral neuropathy (CIPN), 14 with human immunodeficiency virus-associated sensory neuropathy (HIV-SN), and 20 healthy controls (HCs), underwent CCM for estimation of corneal nerve fiber density (CNFD), CNFL, corneal nerve branch density (CNBD), CNFrD, and CNFrD adjusted for CNFL (ACNFrD). RESULTS: In patients with DPN, CIDP, CIPN, or HIV-SN compared to HCs, CNFD (P = 0.004–0.0001) and CNFL (P = 0.05–0.0001) were significantly lower, with a further significant reduction among subgroups. CNFrD was significantly lower in patients with CIDP compared to HCs and patients with HIV-SN (P = 0.02–0.0009) and in patients with DPN compared to HCs and patients with HIV-SN, CIPN, or CIDP (P = 0.001–0.0001). ACNFrD was lower in patients with CIPN, CIDP, or DPN compared to HCs (P = 0.03–0.0001) and in patients with DPN compared to those with HIV-SN, CIPN, or CIDP (P = 0.01–0.005). CONCLUSIONS: CNFrD can detect a distinct pattern of corneal nerve loss in patients with DPN or CIDP compared to those with CIPN or HIV-SN and controls. TRANSLATIONAL RELEVANCE: Various peripheral neuropathies are characterized by a comparable degree of corneal nerve loss. Assessment of corneal nerve topology by CNFrD could be useful in differentiating neuropathies based on the pattern of loss.