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Review
. 2021 Sep 30:2021:6628923.
doi: 10.1155/2021/6628923. eCollection 2021.

Tear Levels of Inflammatory Cytokines in Keratoconus: A Meta-Analysis of Case-Control and Cross-Sectional Studies

Huan Zhang  1 , Xiupeng Cao  2 , Ying Liu  3 , Peihong Wang  1 , Xuan Li  1   4   5
Affiliations
Review

Tear Levels of Inflammatory Cytokines in Keratoconus: A Meta-Analysis of Case-Control and Cross-Sectional Studies

Huan Zhang et al. Biomed Res Int. .

Abstract

Purpose: To assess the tear levels of inflammatory cytokines in patients with keratoconus (KC).

Design: Systemic review and meta-analysis.

Methods: The following electronic databases and search engine were searched: PubMed, EMBASE, Web of Science, and Google Scholar. A systematic search of all relevant studies published through January 2021 was conducted, and the standardized mean difference (SMD) and 95% confidence interval (CI) of cytokine levels were calculated to estimate the pooled effects. Sensitivity analysis, subgroup analysis, and metaregression were applied to explore the sources of heterogeneity.

Results: A total of 7 studies with 374 participants (374 eyes) from clinical studies were included. The tear levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were significantly increased in KC compared with normal controls. The SMD of IL-1β was 1.93 (95% CI 0.22 to 3.65, P = 0.03). The SMD of IL-6 was 1.22 (95% CI 0.59 to 1.84, P < 0.001). The SMD of TNF-α was 1.75 (95% CI 0.66 to 2.83, P = 0.002). There was no significant difference between the two groups on interleukin-4 (IL-4) and interleukin-10 (IL-10). The SMD for IL-4 was 2.36 (95% CI -0.28 to 5.00, P = 0.08) and for IL-10 was 0.30 (95% CI -1.29 to 1.89, P = 0.71). Meta-regression analysis indicated that the heterogeneity maybe significantly correlated with the method of detection, the different ages, and the source of population.

Conclusions: Our meta-analysis demonstrated that proinflammatory cytokines IL-1β, IL-6, and TNF-α were increased, indicating that cytokine profile changed in KC tears and inflammation may play an important role in the pathogenesis and development of KC.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Flow of studies through the meta-analysis.
Figure 2
Figure 2
Forest plot for SMD and 95% CI of IL-1β in tears by keratoconus versus the control group. (a) The pooled effect of IL-1β in all studies. (b–d) Sensitivity analysis of IL-1β in tears by omitting one study in each turn. (e) Subgroup analysis of IL-1β in tears by detection methods.
Figure 3
Figure 3
Forest plot for SMD and 95% CI of IL-4 in tears by keratoconus versus the control group. (a) The pooled effect of IL-4 in all studies. (b) Sensitivity analysis of IL-4 in tears by omitting one study in each turn. (c) Subgroup analysis of IL-4 in tears by detection methods.
Figure 4
Figure 4
Forest plot for SMD and 95% CI of IL-6 in tears by keratoconus versus the control group. (a) The pooled effect of IL-6 in all studies. (b) Sensitivity analysis of IL-6 in tears by omitting one study in each turn. (c) Subgroup analysis of IL-6 in tears by detection methods.
Figure 5
Figure 5
Forest plot for SMD and 95% CI of IL-10 in tears by keratoconus versus the control group. (a) The pooled effect of IL-10 in all studies. (b) Sensitivity analysis of IL-10 in tears by omitting one study in each turn. (c) Subgroup analysis of IL-10 in tears by detection methods.
Figure 6
Figure 6
Forest plot for SMD and 95% CI of TNF-α in tears by keratoconus versus the control group. (a) The pooled effect of TNF-α in all studies. (b) Sensitivity analysis of TNF-α in tears by omitting one study in each turn. (c) Subgroup analysis of TNF-α in tears by detection methods.
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