Subbasal Nerve Plexus Changes in Type 2 Diabetes Mellitus Correlate with Tear Levels of IGFBP-3




Stuard, Whitney L.

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INTRODUCTION: Changes in the corneal subbasal nerve plexus have been reported in patients with Type 2 Diabetes Mellitus (T2DM) and suggest that these changes may provide an early, surrogate marker for the onset of peripheral neuropathy. Increasing studies are investigating the use of tear film biomarkers that correlate with corneal nerve changes in diabetic disease. Our prior studies have demonstrated that the primary insulin-like growth factor (IGF)-1 binding protein, IGF-binding protein-3 (IGFBP-3), is elevated in the diabetic tear film. This study examined tear levels of IGFBP-3 in basal tears of patients with T2DM compared to age, sex, and obesity-matched controls; and assessed the relationship between tear levels of IGFBP-3 with morphological changes in the subbasal nerve plexus and corneal epithelial cells. METHODS: This study is a single visit, cross-sectional study comparing two groups: 1) T2DM and 2) healthy controls. A physician diagnosis of T2DM was required for inclusion in this test group. Groups were matched for age, sex, and obesity status. Each volunteer underwent serology testing for Hemoglobin A1c and high sensitivity C-reactive protein, completed the ocular surface disease index (OSDI) questionnaire and clinical measurements of dry eye, assessment of anthropometric parameters, tear analysis, in vivo confocal microscopy to assess corneal nerve morphology, corneal sensitivity testing, and ocular coherence tomography to assess the retinal nerve fiber layer and macula. Anthropometric measurements were used to calculate BMI and waist to height ratio. Human tears were collected for the analysis of tear levels of IGFBP-3 using an IGFBP-3 Quantikine ELISA kit (R&D Systems, Minneapolis, MN). Confocal data was analyzed using ImageJ and MetaMorph Software. RESULTS: A total of 40 participants were included in this study. There were no differences in corneal sensitivity or dry eye parameters between groups. IGFBP-3 levels in tears of T2DM patients were 3.5 times higher than controls (P<0.05). HbA1c was not correlated to IGFBP-3 (R=0.318, P=0.062). Tear levels of IGFBP-3 were correlated with nerve fiber length (R=0.522 P=0.001) and nerve branch density (R=0.481 P=0.003). IGFBP-3 was more tightly correlated with nerve changes than HbA1c. Consistent with our animal models, there was a decrease in corneal basal epithelial cell density in T2DM compared to controls (P=0.04). DISCUSSION: This study demonstrates that IGFBP-3 is higher in patients with T2DM. These studies further suggest that tear levels of IGFBP-3 may be a novel biomarker for monitoring ocular damage in diabetes. Further studies are needed to stratify tear levels of IGFBP-3 with severity of disease.

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The 56th Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, January 23, 2018, 2-5 p.m., D1.600)

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Stuard, W. L., Titone, R., & Robertson, D. M. (2018, January 23). Subbasal nerve plexus changes in type 2 diabetes mellitus correlate with tear levels of IGFBP-3. Poster session presented at the 56th Annual Medical Student Research Forum, Dallas, TX. Retrieved from

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