Comparison of tear cytokines and neuropeptides, ocular surface parameters, and corneal nerve structure in patients with early-stage diabetes mellitus and control subjects

Purpose: This study aimed to assess the impact of diabetes mellitus (DM) on the corneal nerve, ocular surface, and tear cytokine and substance P (SP) levels and to compare the findings with those in control subjects. Methods: This cross-sectional study included 23 patients diagnosed with DM within the last 5 years and who had no systemic involvement, including diabetic retinopathy, and 22 control subjects. The ocular surface and tear film were assessed using the Ocular Surface Disease Index (OSDI) questionnaire, ocular surface staining, Schirmer, and corneal sensitivity. In vivo confocal microscopy was used to assess the architecture of the corneal nerves. The tear levels of cytokines were examined by Luminex and SP levels were measured by ELISA. Results: Both groups had similar OSDI scores, ocular surface staining, Schirmer, and corneal sensitivity measurements. The patient group had higher corneal nerve tortuosity (p = 0.015) but showed no significant difference in short or long nerve fibre density compared with the control group. Tear IL-6 and IL-8 levels were higher in the DM group (p = 0.002 and p = 0.01, respectively), whereas tear SP levels were lower in the DM group (p = 0.05). The tear SP level exhibited a strong positive correlation with total and long nerve fibre parameters (both p = 0.00). Conclusions: The study results indicated that DM affected corneal nerve structure, tear SP, and inflammatory cytokine levels. The corneal nerves were affected and the tear SP level decreased even in patients without peripheral neuropathy, which is one of the most common complications of DM. In addition, ocular surface inflammation was observed in patients with DM, despite no ocular surface symptoms.