Distinct relationships between secreted factors measured in matched tear fluid, aqueous, vitreous, and plasma samples...

Samples collected using non- or minimally-invasive methods are ideal for biomarker monitoring in patients with retinal conditions. Hence, we determined the relationship of secreted factors (SFs) among tear fluid (TF), aqueous humor (AH), vitreous humor (VH), and plasma samples. 22 patients undergoing vitrectomy for indicated retinal conditions were recruited for the study. Matched TF, AH, VH, and plasma were collected from study subjects without deviation from standard-of-care. Levels of 53 SFs, including immuno-inflammatory and angiogenic factors, were measured using bead-based multiplex ELISA. The total protein concentration of samples was used to adjust and normalize SFs concentration across different sample types and study subjects. Statistical analyses were performed to determine the status and association of the SFs across the matched sample types. The absolute concentrations for the majority of SFs were significantly different between one or more of the four sample types, with the plasma profile being more distinct compared to the other three ocular samples. However, strong positive correlations (r = 0.5 to 0.972) were observed in the concentration between the sample types in over 80 % of the associations. Levels of 28 % of SFs were positively correlated among the 4 sample types. Levels of 30 % - 38 % SFs positively correlated between the three samples (TF-AH-VH; TF-AH-P; AH-VH-P; TF-VH-P). Levels of 79 % of SFs positively correlated with AH-VH, followed by AH-P, 60 %; TF-AH, 55 %; TF-P, 53 %; TF-VH, 45 %; and VH-P, 43 %. Current findings provide evidence for factor-specific use of surrogate sample types (e.g., AH for VH; TF for AH/VH/plasma) for biomarker monitoring or secondary endpoint measurements in patients.