Quantitative analysis of tear angiogenic factors in retinopathy of prematurity: a pilot biomarker study.

Purpose: To determine whether vascular endothelial growth factor (VEGF), angiopoeitin-1 (Ang-1), angiopoetin-2 (Ang-2), and matrix metalloproteinase-9 (MMP-9) can be reliably collected and analyzed from infant tears to aid in the diagnosis of retinopathy of prematurity (ROP) and enhance the ability to objectively monitor its clinical course.

Methods: In this nonrandomized controlled investigation, tear and saliva samples collected from 20 premature infants during serial ophthalmic examination were analyzed using enzyme-linked immunoassay with results analyzed as a function of disease stage and need for treatment.

Results: Tear volume was directly correlated with corrected gestational age (P < 0.001). Tear VEGF levels from samples corresponding to stage 3 ROP were 47.9% lower (P = 0.006) than in samples corresponding to stage 0-1 and 49.1% lower (P = 0.01) than in samples corresponding to stage 2 ROP. There were no between-group differences after normalizing tear VEGF by saliva VEGF levels. Tear/saliva ratio for Ang-1 was 200% greater (P = 0.042) and tear/saliva ratio for Ang-2 was 165% greater (P = 0.035) in samples corresponding to stage 2 versus stage 0-1 ROP disease. Ang-1/Ang-2 ratio was lower in samples from infants who developed stage 2 or worse ROP than in samples from infants who never developed worse than stage 1 ROP (P = 0.031).

Conclusions: In this study cohort, cytokines involved in the pathophysiology of ROP could be reliably identified in and analyzed from infant tears, and showed variation with ROP severity.