Neurofilaments in Tears as Early Biomarkers of Corneal Neurodegeneration in Diabetes Without Retinopathy

Background: Neurodegeneration in the cornea, particularly in diabetic patients, is an emerging area of research that highlights the potential of tear fluid as a source of biomarkers. Neurofilaments light chain (Nf-L), which are structural proteins found in neurons, have been identified as promising candidates for early biomarkers of neurodegeneration. Objective: This study investigates the correlation Nf-L levels in tears and corneal in vivo confocal microscopy (IVCM) parameters in patients with diabetes mellitus without retinopathy with the aim of associating Nf-L level with corneal neurodegeneration. Design: Case-control observational study. Methods: We enrolled 20 patients with diabetes mellitus type 2 (DM) and 20 healthy controls (HC): we studied the levels of Nf-L in serum and tears, and we looked for a correlation with the parameters detected on IVCM, including corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD) and corneal nerve branching density (CNBD). Results: Serum Nf-L levels showed no difference between DM (mean ± SD 14.00 ± 2.18 pg/mL) and HC (mean ± SD 15.18 ± 2.28 pg/mL). Instead we detected a significant increase in Nf-L levels in DM tears (right eye mean ± SD 321.23 ± 192.40 pg/mL; left eye mean ± SD 277.90 ± 254.23 pg/mL) compared to HC (right eye mean ± SD 25.80 ± 22.0 pg/mL; left eye mean ± SD 27.96 ± 20.21 pg/mL). Furthermore, a negative correlation was evident between Nf-L levels and IVCM parameters: CNFL/Nf-L r −.4234 P < .001; CNFD/Nf-L −.4959 P < .001; CNBD/Nf-L r −.5310 P < .0005. Conclusion: Our findings indicate that Nf-L levels are significantly elevated in the tears of DM patients and that high Nf-L levels correlate with lower corneal IVCM parameters, suggesting that tears Nf-L could be a reliable biomarker for early corneal neurodegeneration in diabetes without retinopathy.