Imbalance of Matrix Metalloproteinases and Their Inhibitors Is Correlated With Trabeculectomy Outcomes in Acute Primary Angle Closure

Abstract

To analyze matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and their molar ratios in the aqueous humor in previous acute primary angle closure (APAC) patients and their correlations with trabeculectomy outcomes. Prospective cohort study. Aqueous humor samples were collected from a total of 78 eyes, including 52 previous APAC eyes and 26 cataract eyes. TIMP-1, 2, 3, and 4 and MMP-1, 2, 3, 7, 8, 9, 12, and 13 analyte concentrations were measured using multiplexed immunoassay kits. Patient follow-up occurred at 1week and 1, 3, 6, 12, and 18months. In the previous APAC group, 11 MMP/TIMP molar ratios were significantly lower. APAC eyes were then followed for up to 18months after trabeculectomy and divided into success (37 eyes) and failure (15 eyes) groups. Five out of the 11 molar ratios were significantly lower in the failure group than in the success group. In multiple logistic regression analysis, failed filtration surgery was more likely in APAC eyes with lower MMP-2/TIMP-2 (P= .040, odds ratio= 44.499) and MMP-13/TIMP-1 (P= .034, odds ratio= 37.947) ratios. Previous APAC eyes were divided according to MMP-2/TIMP-2 and MMP-13/TIMP-1 ratios. Compared to eyes with high ratios, eyes with low MMP-2/TIMP-2 and MMP-13/TIMP-1 ratios had significantly higher failure rates. In previous APAC eyes, changes in MMP and TIMP levels resulted in MMP and TIMP imbalance. Lower MMP-2/TIMP-2 and MMP-13/TIMP-1 ratios in aqueous humor are risk factors for trabeculectomy failure. Modulating specific MMP/TIMP ratios may have potential clinical applications for filtration surgery.