Lactoferrin concentration in human tears and ocular diseases: a meta-analysis

Purpose: To evaluate the potential of lactoferrin (Lf) as a diagnostic biomarker for ocular diseases using a meta-analytic approach. Methods: All original studies reporting an estimate of the average Lf concentration in healthy subjects and those affected by ocular diseases were searched up to March 2020. The DerSimonian and Laird method was used to calculate the random effects pooled mean difference and the corresponding 95% confidence interval (CI) in Lf concentration between healthy subjects and those affected by dry eye (DE), Sjögren syndrome (SS), and diabetic retinopathy, separately. The presence of between-study heterogeneity was evaluated using the Cochran's Q test and the I2 index. Stratified analyses were performed to assess potential sources of heterogeneity and influence and cumulative analyses to evaluate the robustness of the results obtained. Publication bias was also evaluated using funnel plot and the Egger's test. Results: The pooled mean differences in Lf concentrations between healthy subjects and those with DE, Sjögren syndrome, and diabetic retinopathy were respectively 0.62 (95% CI, 0.35–0.89) for DE, 3.78 (95% CI, −6.64 to 14.17), and 0.19 (95% CI, −4.00 to 4.39). Regarding DE, the stratified analysis showed that geographical area (P value Q test < 0.0001) and sample size (P < 0.0005) were sources of heterogeneity. Moreover, no study substantially influenced the results obtained and the pooled mean difference became statistically significant after a sample size of 220. Publication bias may affect the results of DE. Conclusions: The results of the current meta-analysis suggest that Lf level in tears is a good candidate as dry eye syndrome diagnostic biomarker.