In vivo Corneal Confocal Microscopy and Nerve Growth Factor in Diabetic Microvascular Complications

Background In vivo corneal confocal microscopy (IVCCM) is being recognized as a non-invasive, early diagnostic tool for diabetic neuropathy, for it provides a clear image of corneal subbasal nerve plexus in detail. Nerve growth factors (NGF) are believed to regulate peripheral and central nervous system, neuronal differentiation, and regeneration of damaged nerves, and their role in diabetic neuropathy is being emphasized these days. Moreover, NGFs and receptors are also expressed in retina and renal mesangial cells, suggesting their possible role in the common pathogenesis of diabetic microvascular complications. We plan to examine corneal structures of diabetic patients and compare IVCCM with conventional tools and analyze their serum and tear NGF levels. Methods IVCCM, nerve conduction velocity (NCV), and serum, urine, and tear samplings were done to 42 diabetic patients. From IVCCM, we measured corneal nerve density, branch, and tortuosity, total corneal/epithelial thickness, and the number of endothelial/keratocyte cells, and we checked patients' biochemical profiles and serum and tear NGF levels. Results Patients with more severe neuropathy had less corneal endothelial cells (3105 ± 218 vs. 2537 ± 142 vs. 2350 ± 73/mm3 vs. 1914 ± 465/mm3,P = 0.02), higher serum NGF (36 ± 15 vs. 60 ± 57.66 vs. 80 ± 57.63 vs. 109 ± 60.81 pg/mL, P = 0.39) and tear NGF levels (135.00 ± 11.94 vs. 304.29 ± 242.44 vs. 538.50 ± 251.92 vs. 719.50 ± 92.63 pg/mL, P = 0.01). There was a positive correlation between neuropathy and corneal nerve tortuosity (r2 = 0.479, P = 0.044) and negative correlation between neuropathy and endothelial cell count (r2 = -0.709, P = 0.002). Interestingly, similar changes were seen in other microvascular complications as well. Conclusion Our results provide a possibility of using novel tools, IVCCM and NGF, as common diagnostic tools for diabetic microvascular complications, but it should be followed by a large population study.ope