Browsing by Subject "Dry Eye Syndromes"
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Item 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.Item More Than Meets the Eye: The Relationship Between Dry Eye Disease and Multisystem Exocrinopathy(2018-01-23) Haque, Waqas; Al-Hashimi, Ibtisam; Robertson, Danielle M.INTRODUCTION: Sjögren's Syndrome, commonly known to be the disease of "dry eyes and dry mouth", is an autoimmune disease that targets the lacrimal and salivary glands. Sjögren's Syndrome primarily affects women with an estimated prevalence of 1.4% in the United States. Its diagnosis is confirmed via presence of anti-Ro/anti-La antibodies, demonstration of reduced salivary and tear production, and a positive lip biopsy. Patients with Sjögren's Syndrome commonly manifest symptoms of a multisystem exocrinopathy. Currently, over 16 million American adults suffer from dry eye disease and do not meet the diagnostic criteria for Sjögren's Syndrome. For many of these patients, current treatment strategies are not sufficient to eradicate or reduce the chronic symptoms of dry eye, thus decreasing overall quality of life. The objective of this study is to establish whether patients with non-Sjögren's dry eye disease also exhibit symptoms of a multisystem exocrinopathy. METHODS: This was a retrospective chart review of 199 randomly chosen patients who were seen between January 2015 and April 2017 in the Department of Ophthalmology at the Aston Ambulatory Care Center. All patients reviewed had a diagnosis of dry eye disease in their medical chart. Using a validated exocrine dysfunction questionnaire as a template, comprehensive data was collected for ophthalmic findings, patient demographics, oral and topical medications, serology, a review of symptoms for all body systems (such as allergies, congestion, and reflux), and all known diagnoses. A univariate analysis was performed to test for differences between dry eye subtypes. A multivariate analysis is currently underway. Results: 31.2% of patients presented with a diagnosis of evaporative dry eye, 57.5% were aqueous-deficient non-Sjögren's dry eye, and 11.3% were aqueous-deficient Sjögren's dry eye. Analysis of the non-Sjögren's cohorts revealed over 25 symptoms consistent with a multisystem exocrinopathy. 35% of dry eye patients had a diagnosis for rheumatoid arthritis. Exocrine manifestations were significantly different among dry eye subtypes for sinusitis (p=0.0283), diarrhea (p=.0059), and hypothyroidism (p=.0291). DISCUSSION: This study is the first to indicate a multisystem exocrinopathy disorder in patients with non-Sjögren's dry eye disease. While results from the multivariate analysis are still pending, the identification of specific exocrine symptoms in patients with distinct subtypes of dry eye may lead to the establishment of new, tailored treatment regimens that will enhance patient response to therapy and improve overall quality of life.Item [Southwestern News](2002-07-12) Echeverria, IoneItem 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.Item [UT Southwestern Medical Center News](2007-08-20) Rian, Russell