Dry eye disease and uveitis: A closer look at immune mechanisms in animal models of two ocular autoimmune diseases

Bose, Tanima; Diedrichs-Möhring, Maria; Wildner, Gerhild

doi:10.1016/j.autrev.2016.09.001

Cited by 50 publications

(34 citation statements)

References 208 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…24–28 Ocular inflammation, of course, can be part of many diseases and, therefore, is not diagnostic of DED, but it may be useful to determine severity, and has been used in clinical trials and other studies to evaluate efficacy of treatment (listed in Tables 1–6). For inflammatory biomarker studies on DED patients, two approaches have primarily been used: impression cytology (IC) and tear sampling.…”

Section: Biomarkers Of Inflammationmentioning

confidence: 99%

The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

Roy

Wei

Kuklinski

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PurposeBiomarkers with minimally invasive and reproducible objective metrics provide the key to future paradigm shifts in understanding of the underlying causes of dry eye disease (DED) and approaches to treatment of DED. We review biomarkers and their validity in providing objective metrics for DED clinical research and patient care.MethodsThe English-language literature in PubMed primarily over the last decade was surveyed for studies related to identification of biomarkers of DED: (1) inflammation, (2) point-of-care, (3) ocular imaging, and (4) genetics. Relevant studies in each group were individually evaluated for (1) methodological and analytical details, (2) data and concordance with other similar studies, and (3) potential to serve as validated biomarkers with objective metrics.ResultsSignificant work has been done to identify biomarkers for DED clinical trials and for patient care. Interstudy variation among studies dealing with the same biomarker type was high. This could be attributed to biologic variations and/or differences in processing, and data analysis. Correlation with other signs and symptoms of DED was not always clear or present.ConclusionsMany of the biomarkers reviewed show the potential to serve as validated and objective metrics for clinical research and patient care in DED. Interstudy variation for a given biomarker emphasizes the need for detailed reporting of study methodology, including information on subject characteristics, quality control, processing, and analysis methods to optimize development of nonsubjective metrics. Biomarker development offers a rich opportunity to significantly move forward clinical research and patient care in DED.OverviewDED is an unmet medical need — a chronic pain syndrome associated with variable vision that affects quality of life, is common with advancing age, interferes with the comfortable use of contact lenses, and can diminish results of eye surgeries, such as cataract extraction, LASIK, and glaucoma procedures. It is a worldwide medical challenge with a prevalence rate ranging from 8% to 50%. Many clinicians and researchers across the globe are searching for better answers to understand the mechanisms related to the development and chronicity of DED. Though there have been many clinical trials for DED, few new treatments have emerged over the last decade. Biomarkers may provide the needed breakthrough to propel our understanding of DED to the next level and the potential to realize our goal of truly personalized medicine based on scientific evidence. Clinical trials and research on DED have suffered from the lack of validated biomarkers and less than objective and reproducible endpoints. Current work on biomarkers has provided the groundwork to move forward. This review highlights primarily ocular biomarkers that have been investigated for use in DED, discusses the methodologic outcomes in providing objective metrics for clinical research, and suggests recommendations for further work.

show abstract

Section: Biomarkers Of Inflammationmentioning

confidence: 99%

The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

Roy

Wei

Kuklinski

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…Uveitis and dry eye disease (DED) share similar inflammatory pathophysiology, including the cytokine activation of interleukin and TNF, 17,18 and the existence of DED leads to corneal damage. 19 Additionally, the dysfunctional immune system in autoimmune diseases can induce the development of both uveitis and corneal diseases. 12 Accordingly, a correlation between uveitis and corneal diseases may be possible and needs to be verified.…”

mentioning

confidence: 99%

Effect of Uveitis on the Development of Keratopathy: A Population-Based Cohort Study

Nien

Lee

Chao

et al. 2018

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

The purpose of this study was to evaluate the effect of uveitis on the development of various keratopathies via the use of the National Health Insurance Research Database (NHIRD) in Taiwan. METHODS. Approximately 1 million patients were randomly sampled from the registry of the NHIRD. Patients diagnosed with uveitis by ophthalmologists were enrolled in the study group after exclusion. Each individual in the study group was age and sex matched to four nonuveitis individuals who serve as the control group. In addition to keratopathy, other possible risk factors and medications were included in the multivariate model, and the effects of different subtypes of uveitis for developing keratopathies were also analyzed. RESULTS. A total of 4773 uveitis patients (2662 male and 2111 female) and 19,092 non-uveitis patients (10,648 male and 8444 female) were enrolled. There were 406 events of keratopathy in the study group, and another 764 events occurred in the control group. A higher incidence rate was found in the study group after adjustment (adjusted hazard ratio [aHR]: 1.772), with a greater cumulative probability (P < 0.0001). For the subgroup analysis, anterior uveitis (aHR ¼ 1.765) and panuveitis (aHR ¼ 3.386) increased the risk of developing keratopathies. Moreover, male sex was associated with a higher aHR than female sex for developing keratopathies in the study group. CONCLUSIONS. The presence of uveitis significantly elevates the risk for developing keratopathy.

show abstract

“…Sjögren's syndrome (SS) dry eye Sjögren's syndrome (SS), a multisystem autoimmune disease, is characterized by lymphocytic infiltration in salivary and lacrimal glands (LGs) and the presence of various autoantibodies (such as anti-Ro(SS-A) or anti-La(SS-B)), resulting in oral and ocular dryness [67,68]. This condition leads to one of the most severe subtypes of dry eye diseases [20]. Activation of both innate and adaptive immune pathways, such as interferon (IFN) signatures, B cell activating factor (BAFF)/BAFF receptor axis, and NF-kB signaling, contributes to the pathogenesis of SS [69,70].…”

Section: Exosomes In Immune-mediated Eye Diseasesmentioning

confidence: 99%

“…The eye, a unique sensory organ of vision, is regarded as an immune-privileged site that prevents immunogenic inflammation [18]. Still, there are several inflammatory and immune-mediated diseases which involve the anterior or posterior segment of the eye, even in severe cases resulting in sight-threatening conditions, such as Sjögren's syndrome (SS) dry eye, corneal allograft rejection, uveitis, and age-related macular degeneration (AMD) [19][20][21]. Of these diseases, the action of immune cells and the expression of pro-inflammatory cytokines and chemokines induce local inflammatory responses which ultimately cause ocular tissue damage.…”

Section: Introductionmentioning

confidence: 99%

Recent advances of exosomes in immune-mediated eye diseases

Zhao

Wei

et al. 2019

Stem Cell Res Ther

View full text Add to dashboard Cite

Exosomes, nanosized extracellular vesicles of 30–150 nm, are shed by almost all cell types. Bearing proteins, lipids, RNAs, and DNAs, exosomes have emerged as vital biological mediators in cell-to-cell communication, affecting a plethora of physiological and pathological processes. Particularly, mounting evidence indicates that immunologically active exosomes can regulate both innate and adaptive immune responses. Herein, we review recent advances in the research of exosomes in several immune-mediated eye diseases, including Sjögren’s syndrome (SS) dry eye, corneal allograft rejection, autoimmune uveitis, and age-related macular degeneration (AMD). Additionally, we discuss the potential of exosomes as novel biomarkers and drug delivery vesicles for the diagnosis and treatment of eye diseases.

show abstract

Dry eye disease and uveitis: A closer look at immune mechanisms in animal models of two ocular autoimmune diseases

Cited by 50 publications

References 208 publications

The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

Effect of Uveitis on the Development of Keratopathy: A Population-Based Cohort Study

Recent advances of exosomes in immune-mediated eye diseases

Contact Info

Product

Resources

About