Dataset Information

TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model.

ABSTRACT: Dry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This inflammation of the LFU ultimately results in tissue deterioration and the symptoms of DED. Moreover, an increase of pathogenic lymphocyte infiltration and the secretion of pro-inflammatory cytokines are involved in the propagation of DED-associated inflammation. Studies have demonstrated that the adoptive transfer of regulatory T cells (Tregs) can mediate the inflammation caused by pathogenic lymphocytes. Thus, as an approach to treating the inflammation associated with DED, we hypothesized that it was possible to enrich the body's own endogenous Tregs by locally delivering a specific combination of Treg inducing factors through degradable polymer microspheres (TRI microspheres; TGF-?1, Rapamycin (Rapa), and IL-2). This local controlled release system is capable of shifting the balance of Treg/T effectors and, in turn, preventing key signs of dry eye disease such as aqueous tear secretion, conjunctival goblet cells, epithelial corneal integrity, and reduce the pro-inflammatory cytokine milieu in the tissue.

SUBMITTER: Ratay ML

PROVIDER: S-EPMC5727478 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model.

Ratay Michelle L ML Balmert Stephen C SC Acharya Abhinav P AP Greene Ashlee C AC Meyyappan Thiagarajan T Little Steven R SR

Scientific reports 20171213 1

Dry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This inflammation of the LFU ultimately results in tissue deterioration and the symptoms of DED. Moreover, an increase of pathogenic lymphocyte infiltration an ...[more]

PMID: 29235530

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Project description:ImportanceDepression is more prevalent in patients with dry eye disease (DED) than in the general population; however, the association between severity of DED and depression needs further evaluation.ObjectiveTo investigate the association between depression and severity of DED symptoms and signs, including inflammatory markers.Design, setting, and participantsSecondary cross-sectional and longitudinal analysis performed in April to December 2020 of data from Dry Eye Assessment and Management (DREAM) study, a randomized clinical trial from October 2014 to July 2016 including patients with moderate to severe symptoms and signs of DED. Enrolled from 27 ophthalmology and optometry centers, both academic and private, in 17 US states, 535 patients were followed up for 1 year.ExposureParticipants screened positive for depression if they scored 42 or less on the Mental Component Summary (MCS) of the 36-Item Short Form Health Survey.Main outcomes and measuresSymptoms of DED were assessed by Ocular Surface Disease Index (OSDI) and Brief Ocular Discomfort Index (BODI) and signs assessed by tear film breakup time, Schirmer test, corneal and conjunctival staining, tear osmolarity, and meibomian gland dysfunction at baseline, 6 months, and 12 months. A composite severity sign score was calculated from all 6 signs. Inflammatory markers (cytokines in tears and HLA-DR expression by conjunctival surface cells) were measured for some trial participants. Features of DED were compared between participants with and without depression and adjusted for age, sex, race, visits, and baseline comorbidities.ResultsAmong the 535 participants, mean (SD) age was 58 (13.2) years, 434 participants (81%) were women, and 398 (74.4%) were White. Participants who screened positive for depression had worse DED symptoms by OSDI (effect size = 0.45, P < .001) and BODI (effect size = 0.46, P < .001) and composite DED sign score (effect size = 0.21, P = .006). Lower MCS score (ie, worse depression) was correlated with higher OSDI score (ie, worse DED symptoms) at baseline (Spearman ρ = -0.09, P = .03), 6 months (ρ = -0.20, P < .001), and 12 months (ρ = -0.21, P < .001). Inflammatory markers did not differ by depression status.Conclusions and relevanceDepression was associated with more severe dry eye symptoms and overall signs, suggesting that among patients with moderate to severe DED, those with depression may be likely to have more severe DED. These findings support consideration of depression as a comorbidity when managing patients with DED. Further study is needed to elucidate the relationship.

Project description:PurposeTo evaluate how increasing age is associated with dry eye disease (DED) signs and symptoms in the Dry Eye Assessment and Management (DREAM) study. This study was undertaken to better understand how DED signs and symptoms differ across decades of life with goals to help assess detection and treatment of DED.DesignSecondary analysis of the DREAM study.SubjectsOne hundred twenty, 140, 185, and 90 participants aged < 50, 50 to 59, 60 to 69, and ≥ 70 years, respectively.MethodsWe performed a secondary analysis of data from the DREAM study, a multicenter randomized clinical trial, to evaluate the effect of omega-3 fatty acid supplementation for the treatment of DED. At baseline, 6 months, and 12 months follow-up, participants underwent an assessment of DED symptoms and signs using Ocular Surface Disease Index, Brief Pain Inventory, tear break-up time (TBUT) (in seconds), Schirmer test with anesthesia (mm/5 minutes), conjunctival staining, corneal staining, meibomian gland dysfunction evaluation, and tear osmolarity (mOsm/l). Multivariable generalized linear regression models were used to compare DED symptoms and signs across the 4 age groups among all participants and by sex.Main outcome measuresScores of DED symptoms, individual signs, and composite scores of DED signs.ResultsAmong 535 patients with DED, increasing age was significantly associated with worse TBUT (P = 0.01), corneal staining (P < 0.001), a composite severity score of DED signs (P = 0.007), and tear osmolarity (P = 0.001). Similar significant differences were found across 4 age groups of 334 women in TBUT, corneal staining score, composite severity score of DED signs, and tear osmolarity (all P < 0.05) but not in men.ConclusionWe found that corneal staining, TBUT, tear osmolarity, and a composite severity score of DED signs were significantly more severe with increasing age in women but not in men; worsening symptoms did not increase with increasing age.Financial disclosuresThe author(s) have no proprietary or commercial interest in any materials discussed in this article.

Project description:PurposeCertain systemic conditions are reported to be risk factors for dry eye disease (DED), but their associations with DED severity are not well studied. We evaluated whether systemic conditions reported to be DED risk factors are associated with severity of DED signs and symptoms.DesignSecondary analysis of data from the Dry Eye Assessment and Management Study, a large-scale multicenter randomized clinical trial of patients with moderate to severe DED.ParticipantsFive hundred thirty-five adult patients with moderate to severe DED from 27 United States centers.MethodsPatients reported their medical history at baseline. They underwent ocular surface examinations and symptom evaluation using standardized protocols at baseline, 6 months, and 12 months. We analyzed the associations of systemic conditions (a systemic disease or smoking history) reported as potential DED risk factors with the severity of DED signs and symptoms using generalized linear regression models adjusted by age, gender, race, and visit.Main outcome measuresDry eye disease symptoms assessed using the Ocular Surface Disease Index (OSDI), 6 DED signs (tear film break-up time, anesthetized Schirmer testing, corneal fluorescein staining, conjunctival lissamine green staining, tear osmolarity, and meibomian gland dysfunction), and a composite signs severity score from 0 to 1 (1 = most severe).ResultsThe mean age was 58 years; 81% were women. More severe DED signs were associated significantly with Sjögren syndrome (mean composite signs severity score 0.52 with disease vs. 0.43 without disease; P < 0.001), facial rosacea (0.47 vs. 0.43; P = 0.002), rheumatoid arthritis (0.47 vs. 0.42; P = 0.002), peripheral artery disease (0.50 vs. 0.43; P < 0.001), and daily smoking history (0.45 vs. 0.43; P = 0.047). Thyroid dysfunction, osteoarthritis, diabetes, irritable bowel syndrome, hypercholesterolemia, hypertension, and hypertriglyceridemia were not associated significantly with DED signs. No conditions were associated significantly with OSDI.ConclusionsIn this large, well-characterized cohort of patients with DED assessed under standardized procedures, patients with certain systemic diseases and smoking history showed more severe DED signs compared with patients without the conditions. The profile of significant DED signs varied by systemic condition, reflecting different DED causes. Understanding the systemic conditions and underlying causes that predispose some patients to severe DED can improve management.

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TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model.

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TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model.

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