Tear levels of insulin-like growth factor binding protein 3 correlate with subbasal nerve plexus changes in patients with type 2 diabetes mellitus

Whitney L. Stuard, Rossella Titone, Danielle M. Robertson

Research output: Contribution to journalArticle

8 Scopus citations


PURPOSE. This study investigated the expression of insulin-like growth factor binding protein-3 (IGFBP-3) in basal tears of patients with type 2 diabetes mellitus compared to nondiabetic controls; and correlated tear levels of IGFBP-3 with morphologic changes in the subbasal nerve plexus and density of basal corneal epithelial cells. METHODS. This was a single visit, cross-sectional study. Diabetic and control subjects were matched for age, sex, smoking status, and body mass index. Tear levels of IGFBP-3 were measured using ELISA. Corneal nerve and basal epithelial cell changes were measured using in vivo confocal microscopy. RESULTS. Tear levels of IGFBP-3 were 3.5-fold higher in those with diabetes. Patients with diabetes also showed a reduction in nerve fiber layer, nerve branch density, and corneal basal epithelial cell density. There was no significant difference in corneal sensitivity. IGFBP-3 levels were highly correlated with nerve fiber length and branch density; while hemoglobin (Hb)A1c was only moderately correlated. There were no significant differences in the clinical or subjective signs of dry eye between groups, indicating that tear levels of IGFBP-3 and corneal nerve changes were not due to the presence of mild dry eye. CONCLUSIONS. These findings indicate that tear levels of IGFBP-3 are more tightly correlated to nerve fiber changes in diabetes than HbA1c. Future studies that stratify the severity of diabetic disease with tear levels of IGFBP-3 are needed to validate this finding.

Original languageEnglish (US)
Pages (from-to)6105-6112
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number14
Publication statusPublished - Dec 1 2017



  • Cornea
  • Epithelium
  • IGFBP-3
  • Subbasal nerve plexus
  • T2DM

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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