Reference Estimates of Mean Tear Film Lipid Layer Thickness Measured with LipiView^® and LipiView II^® in Healthy...

Background/Objectives: Tear film lipid layer thickness (LLT) is an important parameter of ocular surface function and can be objectively measured using LipiView ocular surface interferometry. However, reference LLT estimates in clinically healthy populations remain inconsistent. This systematic review and meta-analysis aimed to estimate pooled reference LLT values and explore potential sources of variability. Methods: A systematic search of PubMed, Scopus, and Web of Science was performed according to PRISMA 2020 guidelines. Studies reporting quantitative LLT measurements obtained using LipiView in healthy or clinically screened adults were included. Primary and expanded meta-analyses were conducted using random-effects models, with a fixed-effect model additionally applied as a sensitivity analysis for the primary meta-analysis. Subgroup analyses evaluated the influence of contact-lens use history, age group, and population eligibility criteria. Results: Twelve studies including 451 participants were included. The primary meta-analysis of three reference cohorts (88 participants) showed a pooled mean LLT of 62.59 nm (95% CI: 59.14-66.04 nm). The expanded analysis yielded a comparable pooled mean LLT of 64.41 nm (95% CI: 57.50-71.31 nm), with substantial heterogeneity (I² = 98.71%). Sensitivity analysis in the expanded meta-analysis demonstrated that the pooled estimate was not substantially influenced by any individual study. Exploratory subgroup analyses indicated numerically lower pooled LLT in studies with documented contact-lens exposure and higher pooled LLT in studies with older populations. However, none of the between-subgroup differences reached statistical significance, and these findings should be interpreted cautiously. Conclusions: A pooled mean LLT of approximately 62-64 nm may serve as a reference estimate for clinical interpretation rather than a diagnostic threshold. However, given the substantial clinical and methodological heterogeneity among available studies, this estimate should be interpreted as a descriptive summary of LipiView-derived LLT values rather than a precise biological parameter. Further standardized studies are needed to establish reliable normative values and clinically meaningful diagnostic criteria.