Evaluations of tear protein markers in dry eye disease: repeatability of measurement and correlation with disease.
OBJECTIVE
We characterized tear protein markers in dry eye disease (DED).


METHODS
In this prospective study, based on the ocular surface disease index (OSDI) and corneal staining (CS), 95 DED patients (OSDI ≥13) with increasing CS were enrolled into 3 severity groups: DE1 (CS <4), DE2 (CS 4-7), and DE3 (CS >7), while 25 asymptomatic subjects with no CS were enrolled into the control group (OSDI <13 and CS = 0). Tear fluid was collected at day 0 and day 7 visits, and concentrations of 43 protein markers were measured by multiplexed immunoassay.


RESULTS
We analyzed 22 control and 80 DED subjects. Among 33 markers detectable, good inter-visit repeatability was observed with 25 markers, with intraclass correlation coefficients (ICC) ranging from 0.85-0.60; ICCs were <0.60 in the other 8. Correlation with clinical measures was found with two markers, with absolute partial correlation coefficients >0.40: Interleukin-1 receptor antagonist (IL-1Ra) and IL-8. IL-1Ra and IL-8 correlated with conjunctival staining (0.43, P < 0.001 and 0.35, P < 0.01, respectively), and with Schirmer test (-0.58 and -0.42, P < 0.001). IL-1Ra and IL-8 in DE3 were 4.4- and 2.1-fold higher than in DE1 (P = 0.0001 and 0.0007), and 1.9- and 1.6-fold higher than in DE2 (P = 0.022 and 0.017). IL-1Ra in DE2 was 2.3-fold higher than in DE1 (P = 0.038).


CONCLUSIONS
Tear levels of many immune mediators were highly repeatable between visits in DED. Among them, IL-1Ra and IL-8 were associated with clinical signs and disease severity defined by corneal staining.
La Jolla BioConsulting, San Diego, California 92130, USA. jingfenghuang@yahoo.com
Jing-Feng
JF
Huang
Yi
Y
Zhang
Kay D
KD
Rittenhouse
Eve H
EH
Pickering
Michael T
MT
McDowell
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D015352:Dry Eye Syndromes / Q000175:diagnosis* / Q000378:metabolism; D005136:Eye Proteins / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013666:Tears / Q000737:chemistry*
D015415:Biomarkers; D005136:Eye Proteins; C042434:tear proteins