Oxidized low-density lipoprotein, lipid and calcium aggregates reveal oxidative stress and inflammation in the conjunctiva of glaucoma patients.

PURPOSE: Conjunctival specimens from primary open-angle glaucoma (POAG), exfoliation glaucoma (ExG) patients and controls were histologically analysed for oxidized low-density lipoprotein (ox-LDL), lipid and calcium aggregates. Our goal was to use them as biomarkers of oxidative stress and inflammation and to evaluate their correlation with glaucoma and impact on surgical outcome. METHODS: Conjunctival samples were obtained from POAG (n = 14) and ExG (n = 17) patients and from control subjects (n = 11) operated for macular hole, retinal detachment or strabismus. Immunohistochemistry was performed using the antibody against ox-LDL. Lipids and calcium were analysed by histochemical stainings with Nile red and Alizarin red S, respectively. RESULTS: Immunoreaction for ox-LDL was significantly increased in POAG (p = 0.049) and the number of lipid aggregates was significantly higher in ExG (p = 0.009) when compared to control. When POAG and ExG patients were grouped according to the outcome of deep sclerectomy (DS) surgery, the number of lipid (p < 0.001) and calcium aggregates (p = 0.014) were significantly higher in the conjunctival stroma of patients whose surgery failed within a three-year follow-up period. CONCLUSIONS: The lipid-mediated alterations suggested the presence of oxidative stress and inflammation in the conjunctiva of glaucoma patients. The present data further support the role of oxidative stress and inflammation in the wound healing process leading to excessive scarring and failure in DS surgery.

Conjunctival matrix metalloproteinases and their inhibitors in glaucoma patients.

PURPOSE: Chronic conjunctival inflammation, caused by various reasons, for example long-term use of topical drugs and/or their preservatives, affects the outcome of glaucoma surgery by interfering with wound healing. Matrix metalloproteinases (MMPs) remodel extracellular matrix (ECM) and are involved in the wound healing process. This study was designed to evaluate the conjunctival expression of MMPs and their tissue inhibitors (TIMPs) in the normal eye, primary open-angle glaucoma (POAG) and exfoliation glaucoma (ExG) and whether there is an association between staining intensities and deep sclerectomy outcome. METHODS: Immunohistochemical procedures were performed on conjunctival samples which were obtained from POAG (n=11) and ExG (n=14) patients as well as normal (n=7) subjects. Antibodies against MMPs (MMP-1, -2, -3 and -9) and TIMPs (TIMP-1, -2 and -3) were used. RESULTS: In conjunctival stroma, expression levels of MMP-2 (p=0.047), MMP-3 (p=0.009), MMP-9 (p<0.001), TIMP-1 (p=0.003), TIMP-2 (p<0.001) and TIMP-3 (p<0.001) in ExG and MMP-9 (p=0.008), TIMP-2 (p=0.02) and TIMP-3 (p=0.002) in POAG were significantly increased compared to control. We further found correlations between expression of MMP-1 and MMP-3 and the length of pilocarpine treatment. CONCLUSION: The expression of MMPs and TIMPs is increased in the conjunctiva of POAG and ExG patients having a long history of topical antiglaucoma drops. Antiglaucoma agents and/or their preservatives alter the remodelling balance of ECM in conjunctiva of POAG and ExG eyes. The balance between MMPs and TIMPs may play a crucial role in the conjunctival wound healing process and the outcome of glaucoma surgery.

Conjunctival inflammatory cells and their predictive role for deep sclerectomy in primary open-angle glaucoma and exfoliation glaucoma.

PURPOSE: To investigate the conjunctival inflammatory alterations of patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (ExG) and correlate the findings with the success of deep sclerectomy (DS) surgery and with the patients' medical history. METHODS: Altogether 25 POAG and ExG patients of the prospective DS study were divided, based on the diagnosis and success of the operation, into 4 groups, POAG S (success), POAG F (failure), ExG S, and ExG F. Controls were obtained from other ophthalmologic surgery patients who did not have glaucoma, and their conjunctiva was examined to be normal. Inflammatory cell subtypes in the conjunctiva were identified and quantified by using immunohistochemistry and monoclonal antibodies: CD3 (T-lymphocyte marker), CD4 (T-helper lymphocyte marker), CD8 (T-cytotoxic lymphocyte marker), CD20 (pan-B cell marker), CD38 (plasma cell marker), CD45RA (naïve T-cell marker), and CD68 (macrophage marker). RESULTS: Higher numbers of inflammatory cells were found in the conjunctiva of the glaucoma patients on medical treatment compared with the normal conjunctiva of the controls. Moreover, T-lymphocytes, T-helper lymphocytes, T-cytotoxic lymphocytes, B cells, plasma cells, and macrophages were found in significantly higher numbers in patients in whom DS failed during the follow-up period of 2.5 years than those with surgical success. CONCLUSIONS: High numbers of cytotoxic and helper T-lymphocytes, plasma cells, and macrophages indicate a chronic inflammatory reaction in the conjunctiva of glaucoma patients. The chronic inflammation is most probably owing to the chronic topical treatment of the patients and seems to be a significant risk factor for DS surgery failure.

Mitomycin C-augmented deep sclerectomy in primary open-angle glaucoma and exfoliation glaucoma: a three-year prospective study.

PURPOSE: To investigate the efficacy and safety of mitomycin C (MMC)-augmented deep sclerectomy with implant (DSCI) in primary open-angle glaucoma (POAG) and exfoliation glaucoma (ExG) patients. METHODS: A total of 68 eyes of 68 patients with POAG and ExG were enrolled consecutively to undergo DSCI with MMC (0.4 mg/ml for 2 min). The intraocular pressure (IOP), number of antiglaucoma medications, neodymium:yttrium-aluminum-garnet (Nd:YAG) laser goniopuncture treatments and complications were compared postoperatively after 36- month follow-up. Surgery was considered as a complete success when IOP was <18 mmHg without antiglaucoma medication. RESULTS: Preoperatively the mean IOPs were 23 ± 6 mmHg and 25 ± 8 mmHg, and 13 ± 4 mmHg and 11 ± 4 mmHg in the POAG and ExG groups, respectively, at 36 months. At 36 months, 74% and 73% of surgeries were a complete success in the POAG and ExG group, respectively [not significant (NS)]. Two patients (8%) of the POAG group and one of the ExG group (3%) were receiving antiglaucoma medication at 36 months (NS). Nd:YAG laser goniopuncture was performed more often in the ExG group (87%) than in the POAG group (61%, p = 0.024). Postoperatively choroidal detachment occurred in 16% of eyes in the POAG group and in 11% of eyes in the ExG group (NS). CONCLUSIONS: DSCI with MMC augmentation appears to be as effective in patients with ExG and POAG in lowering IOP to target levels at medium term with few immediate postoperative complications.

Mitomycin-C-augmented deep sclerectomy in patients with primary open-angle glaucoma and exfoliation glaucoma: a 1-year prospective study.

PURPOSE: To investigate the efficacy and safety of mitomycin C (MMC)-augmented deep sclerectomy with implant (DSCI) in patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (ExG). METHODS: A total of 68 eyes of 68 patients with POAG and ExG were enrolled consecutively to undergo DSCI with MMC (0.4 mg/ml for 2 min). The intraocular pressure (IOP), number of antiglaucoma medications, neodymium:yttrium-aluminum-garnet (Nd:YAG) laser goniopunctures and complications were compared postoperatively. Surgery was considered as a complete success when IOP was < 18 mmHg without antiglaucoma medication. RESULTS: Preoperatively, the mean IOPs were 23.1 +/- 5.8 and 25.4 +/- 8.3 mmHg, and 13.8 +/- 6.1 and 11.2 +/- 5.6 mmHg in the POAG and ExG groups, respectively, at 12 months. 77.4% and 75.7% of surgeries were a complete success in the POAG and ExG groups, respectively [not significant (NS)]. Five patients (16.1%) in the POAG group but none in the ExG group (0%) were receiving antiglaucoma medication at 12 months (NS). Nd:YAG laser goniopuncture was performed in 29.0% of eyes in the POAG group and in 55.6% of eyes in the ExG group (p = 0.047). Postoperatively, choroidal detachment occurred in 16.1% of eyes in the POAG group and in 10.8% of eyes in the ExG group (NS). We encountered no serious complications related to MMC use. CONCLUSION: DS with MMC augmentation appears to be equally effective in ExG and POAG patients in lowering IOP to target levels, at least in the short term, with few immediate postoperative complications.