Relationship between Oxidative Stress Biomarkers and Visual Field Progression in Patients with Primary Angle Closure Glaucoma

Abstract

Purpose. To investigate the serum changes of oxidative stress markers and the relationship between these factors and visual field (VF) progression in patients with primary angle closure glaucoma (PACG). Methods. A case-control and a prospective cohort study. A total of 94 patients with PACG and 89 normal controls were enrolled. Furthermore, 94 PACG subjects were followed up for at least two years (once every six months). All participants were evaluated for serum levels of superoxide dismutase (SOD), total antioxidant status (TAS), hydrogen peroxide (H2O2), malondialdehyde (MDA), glutathione peroxidase, glutathione reductase, and detailed eye and systematic examination. Binary logistic regression analysis and Cox regression analysis were performed. Results. The serum levels of SOD and TAS in the PACG group were significantly lower than those in the control group (p<0.001). Meanwhile, PACG subjects had significantly higher levels of MDA and H2O2 than the normal control subjects (p<0.001). Serum levels of TAS (OR=0.773, 95%CI=0.349−0.714, p<0.001), SOD (OR=0.975, 95%CI=0.955−0.995, p<0.001), MDA (OR=1.155, 95%CI=1.080−1.235, p<0.001), and H2O2 (OR=1.216, 95%CI=1.142−1.295, p<0.001) were independent risk/protective factors for PACG. TAS levels (HR=0.041, 95%CI=0.008–0.218, p<0.001), SOD levels (HR=0.983, 95%CI=0.971–0.994, p=0.003), and MDA levels (HR=1.010, 95%CI=1.001–1.018, p=0.015) at baseline were associated with visual field progression. Kaplan–Meier curves reveal that patients with TAS<0.95/SOD<143/MDA>12 had a significantly higher percentage of PACG progression (p<0.05). Conclusions. Decreased levels of TAS and SOD as well as increased levels of MDA at baseline were associated with VF progression in patients with PACG. These findings suggest that oxidative stress was involved in the onset and development of PACG.

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

“…Malondialdehyde (MDA) is a lipid peroxidation product whose levels increase in plasma [ 128 , 129 , 130 , 131 ] and aqueous humor [ 137 , 155 , 190 , 191 ] in patients with glaucoma. Malonyl dialdehyde levels seem to be correlated with the severity of visual field loss in primary angle-closure glaucoma (PACG) and POAG [ 182 , 183 ]; thereby, they are considered to be a good indicator of the glaucoma progression. 8-hydroxy-2′-deoxyguanosine (8-OHdG) is an oxidative product of DNA damage whose levels in serum [ 67 , 132 , 133 , 134 , 135 ] and aqueous humor [ 67 , 134 ] are reported to be higher in glaucoma patients than controls.…”

“…In aqueous humor levels of IL-1β [ 175 , 197 ], IL-8, IP-10 [ 174 ], IL-6 [ 175 , 176 , 177 , 197 ], TNF-α [ 187 , 208 , 209 ], MCP-1 [ 174 ] (24), IL-2, IL-5 [ 175 ], and VEGF [ 169 , 174 , 176 , 177 , 178 ] were higher in patients with certain type of DR compared to controls. Most of the proteins reported in aqueous are correlated with vitreous: IL-6 [ 177 , 179 , 180 , 181 ], VEGF [ 182 , 183 , 184 , 185 ], IL-8 [ 184 , 192 , 194 ], IP-10 [ 186 ], MIP-1β, TNF-α [ 180 ], MCP-1 [ 184 , 192 , 210 ], PlGF [ 180 ], and VEGF. The vitreous and aqueous levels of IL-6 and VEGF were significantly correlated with the severity of diabetic retinopathy and with the pathogenesis of diabetic macular edema [ 183 , 189 , 211 ].…”

“…Most of the proteins reported in aqueous are correlated with vitreous: IL-6 [ 177 , 179 , 180 , 181 ], VEGF [ 182 , 183 , 184 , 185 ], IL-8 [ 184 , 192 , 194 ], IP-10 [ 186 ], MIP-1β, TNF-α [ 180 ], MCP-1 [ 184 , 192 , 210 ], PlGF [ 180 ], and VEGF. The vitreous and aqueous levels of IL-6 and VEGF were significantly correlated with the severity of diabetic retinopathy and with the pathogenesis of diabetic macular edema [ 183 , 189 , 211 ]. On the other hand, proteomics analysis of vitreous and AH shows proteins that participate in a complementary system: clusterin, complement C3, and C4-A, which are factors that can serve as biomarkers for proliferative diabetic retinopathy (PDR) [ 187 ].…”

Candidate Glaucoma Biomarkers: From Proteins to Metabolites, and the Pitfalls to Clinical Applications

“…Upregulation of oxidative stress parameters was observed in the serum of PACG patients (n = 50), although with a slightly increased fold change for MDA, conjugated diene, 4-hydroxynonenal, AOPP, 8-hydroxydeoxyguanosine (8-OHdG), and ischemia-modified ALB, further limiting classification of the disease [ 159 ]. However, in a recent prospective study, the serum levels of SOD and total antioxidant status (TAS) determined spectrophotometrically in PACG patients were significantly lower than those in the control group, while MDA and hydrogen peroxide were higher in individuals with glaucoma, with 5.5- and 2.2-fold change, respectively, suggesting that oxidative stress may be involved in the onset and development of PACG [ 160 ]. Moreover, the analysis of thiol/disulfide homeostasis may indirectly reflect the increase in oxidative stress and DNA damage, along with the ischemia-modified ALB.…”

Methods to Analyse Time‐to‐Event Data: The Kaplan‐Meier Survival Curve

“…To illustrate the application of the K-M method, we consider a prospective cohort study by Li et al [ 6 ]. In this paper, the authors investigated the relationship between oxidative stress biomarkers and visual field progression in patients with primary angle closure glaucoma (PACG).…”