Abstract
Background—It is recognized that inflammation is an underlying cause of dry eye disease (DED), with cytokine release involved. We systematically reviewed literature with meta-analyses to quantitatively summarize the levels of tear cytokines in DED. Methods—The PubMed, Embase, Web of Science, Ovid, Cochrane, and Scopus databases were reviewed until September 2019, and original articles investigating tear cytokines in DED patients were included. Differences of cytokines levels of DED patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed by applying Newcastle-Ottawa-Scale and the GRADE quality score. Methods of analytical procedures were included as covariate. Results—Thirteen articles investigating 342 DED patients and 205 healthy controls were included in the meta-analysis. The overall methodological quality of these studies was moderate. Systematic review of the selected articles revealed that DED patients had higher tear levels of interleukin (IL)-1β, IL-6, chemokine IL-8, IL-10, interferon-γ, IFN-γ, and tumor necrosis factor-α, TNF-α as compared to controls. Evidence was less strong for IL-2 and IL-17A. Conclusions—Data show that levels of tear cytokines in DED and control display a great variability, and further studies of higher quality enrolling a higher number of subjects are needed, to define a cut-off value.
Highlights
Dry eye disease (DED) affects millions of patients worldwide with a prevalence ranging from 5 to 50% and increasing with age [1], and is one of the most frequent causes of visits in the ophthalmic daily practice [2]
The definition of dry eye disease (DED) given in the TFOS DEWS (Tear Film & Ocular Surface Society) II consensus [4] includes inflammation as one of the key elements contributing to the onset and triggering a self-sustaining vicious circle
Recent studies have suggested that pro-inflammatory cytokines in tears exert a key role in the pathogenesis of several ocular surface diseases, including DED [4,5], and Pflugfelder and co-workers demonstrated increased levels of IL-1, IL-6, and IL-8 in Sjogren’s syndrome (SS) patients, and these increased concentrations were associated with the severity of DED clinical parameters, such as greater corneal staining and lower tear secretion [6,7,8]
Summary
Dry eye disease (DED) affects millions of patients worldwide with a prevalence ranging from 5 to 50% and increasing with age [1], and is one of the most frequent causes of visits in the ophthalmic daily practice [2]. TTohkeinaeims aonfdthchisemmeotka-ines in DEaDnaplaytsiiesnwtsaasntdhecroenfotrroelst.o systematically and quantitatively review data on pro-inflammatory cytokines and chemokines in DED patients and controls. We systematically reviewed literature with meta-analyses to quantitatively summarize the levels of tear cytokines in DED. Methods—The PubMed, Embase, Web of Science, Ovid, Cochrane, and Scopus databases were reviewed until September 2019, and original articles investigating tear cytokines in DED patients were included. Systematic review of the selected articles revealed that DED patients had higher tear levels of interleukin (IL)-1β, IL-6, chemokine IL-8, IL-10, interferon-γ, IFN-γ, and tumor necrosis factor-α, TNF-α as compared to controls. Conclusions—Data show that levels of tear cytokines in DED and control display a great variability, and further studies of higher quality enrolling a higher number of subjects are needed, to define a cut-off value
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