Though a number of different cytokines/chemokines have been analyzed in tears of DED patients,
45–47 this review will focus on 4 cytokines that have shown to be consistently elevated in DED tears compared to non-DED controls, and thought to have a mechanistic role in DED: (1) TNF-α for general inflammatory status of the ocular surface
61 (
Table 3), (2) IL-6, which has pro- and anti-inflammatory roles, may provide important information on ocular immune status and on treatment effect
62 (
Table 4), (3) IL-17a, which is secreted by specialized T helper 17 (Th17) subpopulation
63 (
Table 5), and (4) IL-8, which is important in chemotaxis to mediate macrophage and epithelial innate immunity
64 (
Table 6). As can be observed in the Tables
, a wide range of concentrations has been observed for these cytokines. For example, while tears from DED patients tested for IL-8 showed higher mean values for IL-8 compared to normals (
Table 6), the reported concentrations ranged from 74
+ 55 pg/mL
65 to 6518.3
+ 4509.7 pg/mL
66 for DED and from 176
+ 72 pg/mL
67 to 1150
+ 50 pg/mL in normals.
68 While some of the variability, as with IC studies (
Table 2), may be due to biologic variations, the technique used is likely an issue as well. However, the variation in concentrations observed with “normal” subjects is remarkable. It must be noted that under the umbrella of Luminex technology, studies have used assay kits from different manufacturers, different instruments, or even the same instrument with different panels or settings, which may contribute significantly to the wide range of concentrations observed for the same cytokine. Even after the sample processing is completed, data analyzed and reported with different stringent curve fitting models vary significantly, for example, best curve fitting, five-parameter curve fitting, four-parameter curve fitting, cubic spline fitting, or linear polation fitting (Milliplex Analyste User Guide). Few reports describe the analysis algorithm used. Therefore absolute concentrations are likely not comparable between studies and reporting percent change or ratios may be a more useful metric for reporting analyte levels in tears at baseline and with treatment in clinical trials.