The Relationship Between Plasma MMP-9 and TIMP-2 Levels and Intraocular Pressure Elevation in Diabetic Patients After Intravitreal Triamcinolone Injection

Abstract

To find out the relationship between steroid-induced intraocular pressure (IOP) rise and the plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-2 (TIMP-2) in diabetic patients who underwent intravitreal triamcinolone acetonide (IVTA) injection for the treatment of diabetic macular edema. A total of 34 patients with diabetic macular edema who were treated with IVTA and 17 healthy subjects who served as control group for plasma MMP and TIMP levels were participated. Before IVTA treatment, patients and control subjects underwent complete ophthalmologic examination, including best-corrected visual acuity, slit-lamp biomicroscopy, IOP measurement with Goldmann applanation tonometry, and indirect ophthalmoscopy; and peripheral blood samples were collected from each study participants. Plasma levels of MMP-9, TIMP-2, and HbA1c levels were measured. Patients were seen 1, 6, 12, and 24 weeks after treatment and then every 6 months for up to 1 year for probable IOP rise. Patients were divided into 2 groups as having nonproliferative or proliferative diabetic retinopathy. These 2 groups were further classified according to their IOP levels as normal or elevated IOP (>21 mm Hg). The mean age of diabetic group of patients (n=34) and healthy control subjects (n=17) were 57.6+/-10.2 years (range: 22 to 70 y) and 53.1+/-10.3 years (range: 29 to 68 y), respectively. Seventeen (50%) diabetic patients had developed elevated IOP after a mean 2.2 months after IVTA injection. MMP-9 and TIMP-2 levels were found to be significantly higher in the diabetic groups with and without elevated IOP when compared with control group (P<0.001). MMP-9/TIMP-2 did not change significantly among the groups. Logistic regression analysis showed that only higher plasma TIMP-2 levels increase the risk of IOP elevation after IVTA injection in proliferative diabetic retinopathy (odds ratio=1.06, P<0.05). No significant relationship was found between IOP rise and HbA1c levels. The high levels of TIMP in diabetic patients might have a role on steroid-induced IOP rise. The key pathogenetic events that up-regulate TIMP levels should be investigated in steroid IOP rise in diabetics.