Browsing by Subject "Tears"

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The Impact of Diurnal Changes and Inter-Visit Variability on the Concentration of Insulin-Like Growth Factor-1 in Human Tears
(2015-01-26) Patel, Roshni; Zhu, Meifang; Robertson, Danielle M.
INTRODUCTION: There is a growing body of research focused on the use of tear film-derived proteins as biomarkers of disease. Previous studies have reported quantitative changes in tear-derived growth factors and related proteins associated with various systemic and ocular diseases. Major challenges when working with human tears however, includes sample volume limitation and the high potential for reflex tearing. One method of tear collection that is increasingly being reported involves the use of microcapillary tubes to draw tears from the inferior tear reservoir. The purpose of this study was to investigate the impact of diurnal changes and inter-visit variability on the concentration of a known growth factor present in human tears, the insulin-like growth factor-1 (IGF-1). METHODS: Nine healthy volunteers without any reported symptoms of dry eye were recruited for this study. At visit 1 (baseline), all participants underwent a standard dry eye examination to assess tear volume, tear film break up time (TFBUT), and tear production. Subjects were asked to return to clinic for an additional 5 visits (morning and afternoon on a total of 3 days). Tears were collected at the start of each visit from the inferior temporal tear meniscus of both eyes using 1 - 10 μl glass microcapillary tubes and frozen at -80C until use. Total protein was measured for each patient using a bicinchoninic assay. IGF-1 levels wear assessed using ELISAs. RESULTS: 8.8 ± 2.1 μg/μl of total protein was obtained from each subject. Total protein was unchanged at each visit. There was no difference in IGF-1 between morning and afternoon. Tear levels of IGF-1 did vary with visit, with the final visit showing a 2 fold-increase over baseline (p<0.05). Tear levels of IGF-1 were correlated with TFBUT (R=0.856, p=0.007). DISCUSSION: While diurnal variation did not affect basal levels of IGF-1 in tears, there was a visit-dependent increase. This increase was likely due to a reduction in reflex tearing during tear collection as patients became more comfortable with the technique. Similarly, the decrease in IGF-1 that corresponded with increased tear evaporation was likely due to changes in reflex tearing. Together, these findings suggest that low abundant proteins, such as IGF-1, are highly susceptible to changes in reflex tearing. These findings also suggest that a participant training phase may be required.
Subbasal Nerve Plexus Changes in Type 2 Diabetes Mellitus Correlate with Tear Levels of IGFBP-3
(2018-01-23) Stuard, Whitney L.; Titone, Rossella; Robertson, Danielle M.
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.
Tear Biomarkers and Corneal Sensitivity as an Indicator of Neuropathy in Type 2 Diabetes
(2020-05-01T05:00:00.000Z) Iyengar, Meera Farzana; Chang, Mary; Lingvay, Ildiko; Rajora, Nilum
BACKGROUND: Diabetic peripheral neuropathy (DPN) is a debilitating, progressive complication of type 2 diabetes. The high cost of management leads to amputations in approximately 6% of individuals with DPN in poor-resource settings due to medical noncompliance or lack of finances. Having an effective means of early detection of DPN is crucial for early intervention, which would have a major impact in alleviating its social, economic, and medical burden. OBJECTIVES: To explore the potential of 31 tear biomarkers involved in both corneal growth and development and inflammatory pathways in screening for diabetic peripheral neuropathy (DPN). Additionally, the utility of aesthesiometry for measuring corneal damage in DPN was assessed. METHODS: This screening test pilot study recruited 90 participants from a tertiary hospital in Lima, Peru. Participants were categorized into three groups based on diabetes and neuropathy status. Tears were collected on Schirmer strips, and proteins were measured by both ELISA and multiplex-bead assay. Corneal sensitivity was measured by aesthesiometry, and DPN was measured through vibration perception threshold testing. RESULTS: A total of 89 participants were included in the analysis. The mean age was 55.7+1.46, and 58.4% were female. After adjusting for potential confounders, MMP-9 and TGF-alpha levels showed a strong upward trend in participants with DPN when compared to those with diabetes alone, though not significant. Decreased corneal sensitivity, as measured by aesthesiometry, was negatively correlated with MMP-9 levels (p<0.01) in individuals with DPN. Aesthesiometry was significantly decreased in individuals with DPN when compared to participants with diabetes alone (p<0.01) and normal controls (p<0.01). CONCLUSIONS: Although tears are a simple and inexpensive resource with promise to help detect DPN, it is an insufficient standalone tool for detecting DPN based on the present study. Aesthesiometry is a simple, inexpensive, and accurate method to assess corneal damage associated with DPN, and its integration into screening practices has potential to improve detection of DPN in poor-resource settings.