Temporal Variations in Inflammatory-Related Ocular Surface Parameters: A Systematic Review and Meta-Analysis

This systematic review sought to identify, appraise, and synthesize data from studies that investigated inflammatory-related temporal changes, over a 12 ± 4-hour period, in the structure and/or function of ocular surface parameters in healthy individuals.

Comprehensive searches were performed in Ovid MEDLINE and Embase in December 2025. Two authors independently evaluated study eligibility and extracted data. For each parameter, the temporal mean difference (evening minus morning value) was derived. Findings were summarized using narrative syntheses and/or meta-analyses, informed by data availability.

Forty-two studies (36 cross-sectional, 2 non-randomized interventional, and 4 randomized controlled trials, n = 706 participants) were included. There was very limited evidence (n = 1 study, narrative findings) relating to temporal variations in human corneal immune cell density. Neutrophil numbers in the palpebral conjunctiva, tear neutrophil gelatinase-associated lipocalin, and tear matrix metalloproteinase-9 levels were generally higher in the morning (n = 1 study, respectively, narrative findings). Meta-analysis suggested tear polymorphonuclear (PMN) leukocyte cell counts may be relatively higher in the morning (2 studies; mean difference: -6,526; 95% confidence interval [CI] = -8362 to -4691 cells, I2 = 0.00%). The certainty of the evidence (Grading of Recommendations, Assessment, Development and Evaluation [GRADE]) was judged as very low for all outcomes, due to risk-of-bias, insufficient studies, and/or low sample sizes.

Further to the availability of very low certainty evidence, it remains unclear whether the ocular surface inflammatory status in healthy individuals differs in the morning relative to the evening. Further research is required to understand the extent to which temporal factors affect the homeostasis of inflammatory-related ocular surface parameters in healthy individuals.