Impact of Diabetic Peripheral Neuropathy on Corneal Sensitivity and Ocular Surface

Diabetes mellitus (DM) is frequently associated with microvascular complications, including diabetic peripheral neuropathy (DPN). The cornea, one of the most densely innervated tissues in the body, has been proposed as a surrogate marker for small fiber neuropathy. Patients with DM often present with ocular surface disease (OSD) and corneal sensitivity impairment, but the relationship between DPN, ocular surface alterations, and inflammatory biomarkers remains unclear. This study aimed to evaluate ocular surface parameters between patients with type 2 DM with and without DPN and to explore the associations among corneal sensitivity, ocular surface inflammation (matrix metalloproteinase-9 [MMP-9]), and dry eye-related parameters.

In this cross-sectional observational study, 158 eyes of 79 patients with type 2 DM were categorized based on the presence or absence of DPN, diagnosed via electromyography. Corneal sensitivity was evaluated using the Brill esthesiometer, and tear MMP-9 levels were assessed with the InflammaDry test. Additional assessments included the Ocular Surface Disease Index (OSDI), tear osmolarity, Schirmer test, noninvasive tear break-up time, and meibography. Corneal impairment was defined as esthesiometry levels 4-6 or pressure thresholds ≥8 mbar in either eye.

Patients with DPN exhibited significantly reduced corneal sensitivity (6.98 ± 2.25 mbar vs. 5.62 ± 2.53 mbar; p = 0.014) and higher OSDI scores (median 26 vs. 10; p < 0.001). MMP-9 positivity was more common in patients with corneal sensory impairment (81.8% vs. 54.3%; p = 0.0215). A significant negative correlation was observed between tear osmolarity and corneal sensitivity (r = -0.182, p = 0.022). Multivariable regression showed that both DPN (β = 1.20) and MMP-9 positivity (β = 1.24) were independently associated with reduced sensitivity.

Reduced corneal sensitivity was significantly associated with the presence of DPN and with MMP-9 positivity and showed a negative correlation with tear osmolarity. Corneal sensitivity testing combined with tear MMP-9 assessment may provide complementary information on ocular surface changes in diabetic patients, although current variability and limited reproducibility prevent their use as standalone screening tools for neuropathy.