Neurofilaments in Tears as Early Biomarkers of Corneal Neurodegeneration in Diabetes Without Retinopathy
Vincenzo Macaione, Francesca Polito, Giovanni W. Oliverio, Emanuela Aragona, Elisa I. Postorino, Maura Mancini, Paola Palino, M’hammed Aguennouz, Pasquale AragonaBackground:
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
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.