Total Tear IgE Levels Correlate with Allergenic and Irritating Environmental Exposures in Individuals with Dry Eye.

Dry eye (DE) and allergic conjunctivitis may present similarly, and it remains unclear whether some individuals have an underlying allergic component to their DE. To better understand this relationship, we performed a cross-sectional study in 75 individuals with DE symptoms and/or signs. Immunoglobulin E (IgE) levels in tear samples were quantified and home environmental exposures assessed via standardized survey. Tears were collected by Schirmer strip, and total tear IgE levels were quantified using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using descriptive statistics and linear and logistic regressions. The main outcome measures were total tear IgE levels and their association with environmental exposures. The mean age of the subjects was 66.2 ± 7.8 years. Sixty-two individuals had dry eye symptoms (Dry Eye Questionnaire-5 ≥ 6), and 75 had one or more signs of DE. Detectable total tear IgE levels were observed in 76% of subjects, and 17.3% had high levels (>1 ng/mL). Individuals with exposure to pet(s) (odds ratio (OR) 11.5, p = 0.002) and smoke (OR 38.6, p = 0.008) at home were more likely to have high IgE levels compared to those not exposed. Individuals with tears collected during spring or summer were 3.9 times (p = 0.028) more likely to have high IgE compared to those sampled at other times of year. Subjects born in the US were 3.45 times (p = 0.010) more likely to have high IgE compared to individuals born outside the US. To conclude, a majority of individuals with DE symptoms and/or signs had detectable IgE levels in their tears. High tear IgE levels were correlated with allergy season and exposures in the home linked with allergy.

Traumatic brain injury, dry eye and comorbid pain diagnoses in US veterans.

AIMS: The purpose of the study is to evaluate the relationship between dry eye (DE) and pain diagnoses in US veterans with and without traumatic brain injury (TBI). METHODS: Retrospective cohort study of veterans who were seen in the Veterans Administration Hospital (VA) between 1 January 2010 and 31 December 2014. Veterans were separated into two groups by the presence or absence of an International Classification of Diseases, Ninth Revision diagnosis of TBI and assessed for DE and other comorbidities. A dendrogram was used to investigate the linkage between TBI, DE, chronic pain and other comorbid conditions. RESULTS: Of the 3 265 894 veterans seen during the 5-year period, 3.97% carried a diagnosis of TBI. Veterans with TBI were more likely to have a diagnosis of DE compared with their counterparts without TBI (37.2% vs 29.1%, p<0.0005). The association was stronger between TBI and ocular pain (OR 3.08; 95% CI 3.03 to 3.13) compared with tear film dysfunction (OR 1.09; 95% CI 1.07 to 1.10). Those with TBI were also about twice as likely to have a diagnosis of chronic pain, headache, depression or post-traumatic stress disorder compared with their counterparts without TBI. Cluster analysis of TBI, DE and pain diagnoses of interest revealed that central pain syndrome, cluster headache, sicca syndrome, keratoconjunctivitis sicca and late effect of injury to the nervous system (as can be seen after TBI) were all closely clustered together. CONCLUSIONS: DE and pain disorders occur at higher frequencies in patients with a diagnosis of TBI, suggesting a common underlying pathophysiology.

Evidence that dry eye is a comorbid pain condition in a U.S. veteran population.

INTRODUCTION: Recent evidence suggests that dry eye (DE) may be comorbid with other chronic pain conditions. OBJECTIVES: To evaluate DE as a comorbid condition in the U.S. veteran population. METHODS: Retrospective review of veterans seen in the Veterans Administration Healthcare System (Veteran Affairs) between January 1, 2010, and December 31, 2014. Dry eye and nonocular pain disorders were ascertained by International Classification of Diseases, Ninth Revision (ICD-9) codes. Dry eye was further separated into ICD-9 codes representing tear film dysfunction or ocular pain. χ2 and logistic regression analyses were used to examine frequency and risk of DE, ocular pain, and tear film dysfunction by pain disorders. RESULTS: Of 3,265,894 veterans, 959,881 had a DE diagnosis (29.4%). Dry eye frequency increased with the number of pain conditions reported (P < 0.0005). Ocular pain was most strongly associated with headache (odds ratio [OR] 2.98; 95% confidence interval [CI] 2.95-3.01), tension headache (OR 2.64; 95% CI 2.58-2.71), migraine (OR 2.58; 95% CI 2.54-2.61), temporomandibular joint dysfunction (OR 2.39; 95% CI 2.34-2.44), pelvic pain (OR 2.30; 95% CI 2.24-2.37), central pain syndrome (OR 2.24; 95% CI 1.94-2.60), and fibromyalgia/muscle pain (OR 2.23; 95% CI 2.20-2.26), all P < 0.0005. Tear film dysfunction was most closely associated with osteoarthritis (OR 1.97; 95% CI 1.96-1.98) and postherpetic neuralgia (OR 1.95; 95% CI 1.90-2.00), both P < 0.0005. CONCLUSIONS: Dry eye, including both ocular pain and tear film dysfunction, is comorbid with pain conditions in this nationwide population, implying common mechanisms.

Phosphatidylinositol-4-phosphate 5-kinase and GEP100/Brag2 protein mediate antiangiogenic signaling by semaphorin 3E-plexin-D1 through Arf6 protein.

The semaphorins are a family of secreted or membrane-bound proteins that are known to guide axons in the developing nervous system. Genetic evidence revealed that a class III semaphorin, semaphorin 3E (Sema3E), and its receptor Plexin-D1 also control the vascular patterning during development. At the molecular level, we have recently shown that Sema3E acts on Plexin-D1 expressed in endothelial cells, thus initiating a novel antiangiogenic signaling pathway that results in the retraction of filopodia in endothelial tip cells. Sema3E induces the rapid disassembly of integrin-mediated adhesive structures, thereby inhibiting endothelial cell adhesion to the extracellular matrix. This process requires the activation of small GTPase Arf6 (ADP-ribosylation factor 6), which regulates intracellular trafficking of ß1 integrin. However, the molecular mechanisms by which Sema3E-Plexin-D1 activates Arf6 remained to be identified. Here we show that GEP100 (guanine nucleotide exchange protein 100)/Brag2, a guanine nucleotide exchange factor for Arf6, mediates Sema3E-induced Arf6 activation in endothelial cells. We provide evidence that upon activation by Sema3E, Plexin-D1 recruits phosphatidylinositol-4-phosphate 5-kinase, and its enzymatic lipid product, phosphatidylinositol 4,5-bisphosphate, binds to the pleckstrin homology domain of GEP100. Phosphatidylinositol 4,5-bisphosphate binding to GEP100 enhances its guanine nucleotide exchange factor activity toward Arf6, thus resulting in the disassembly of integrin-mediated focal adhesions and endothelial cell collapse. Our present study reveals a novel phospholipid-regulated antiangiogenic signaling pathway whereby Sema3E activates Arf6 through Plexin-D1 and consequently controls integrin-mediated endothelial cell attachment to the extracellular matrix and migration.