A novel oculoplastic surgery for exposed glaucoma drainage shunt by using autologous graft.
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Biomedical subjects
Publications and source records attributed to Markku Teräsvirta.
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BACKGROUND: Hyperhomocysteinemia (HH), oxidative stress and endothelial dysfunction are all implicated as possible pathogenetic factors in exfoliation syndrome (XFS) and exfoliative glaucoma (XFG). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide and plasma level of ADMA is often elevated in HH. Thus the present study was undertaken to study plasma levels of ADMA with concomitant measurement of symmetric dimethylarginine (SDMA) and L-arginine (L-Arg) in XFS and XFG. METHODS: This cross-sectional, prospective study involved 36 XFS patients, 11 of them having XFG, and 36 age- and gender-matched controls. Fasting plasma ADMA, SDMA and L-Arg levels of participants were determined. A special view was created how plasma L-Arg, ADMA and SDMA correlate to plasma homocysteine (P-Hcy). In addition, the influence of P-Hey values derived from our previous study on the above mentioned parameters were evaluated by cut-off values of P-Hcy, 12 micromol/l for women and 14.5 micromol/l for men. RESULTS The mean plasma ADMA, SDMA and L-Arg levels were 0.41, 0.49 and 62.9 micromol/l in the XFS/XFG group, and 0.41, 0.44 and 69.7 micromol/l in the control group, respectively. As all parameters within the XFS and control group were compared, no statistical significance was stated. On the other hand, a positive correlation was observed between plasma SDMA and P-Hcy in XFGs (P = 0.002), and additionally, also a statistically significant difference was in plasma SDMA between the two groups sorted by cut-off levels of P-Hcy 0.49 +/- 0.15 vs. 0.36 +/- 0.04 micromol/l, above and below cut-off levels, respectively (P = 0.001), but not between ADMA in a respective assay. The mean values of L-Arg were 64.6 +/- 17.2 vs. 74.8 +/- 13.3 microg/l, respectively (P = 0.031). In the XFS subgroup, on the contrary, there was no positive correlation between P-Hcy and plasma SDMA. CONCLUSIONS: A positive correlation of plasma SDMA in respect to P-Hcy in XFGs and increase of SDMA in mild or intermediate hyperhomocysteinemia may indicate SDMA as a marker of developing XFG in hyperhomocysteinemic
BACKGROUND: In glaucoma, extensive pathological changes occur in the trabecular meshwork (TM) and juxtacanalicular tissue of the chamber angle. Aqueous humor drainage is disturbed due to the accumulation of extracellular matrix (ECM) material in the outflow system. Matrix metalloproteinases (MMPs) remodel ECM material and, thus, they may have a role in regulating outflow facility and intraocular pressure (IOP). This study examined the expression of MMPs and tissue inhibitors of MMPs (TIMPs) in the chamber angle of normal eyes and in primary open-angle glaucoma (POAG) and in exfoliation glaucoma (ExG). METHODS: TM tissues were isolated from healthy donor eyes for corneal transplantation. Specimens of the inner wall of Schlemm's canal and the juxtacanalicular tissue were collected from patients with POAG or ExG during deep sclerectomy operation. Monoclonal antibodies against MMPs (MMP-1, -2, -3, and -9) and antibodies against TIMPs (TIMP-1, -2, and -3) were used for immunohistochemical staining. RESULTS: Immunoreactivity for MMP-2, TIMP-2, or TIMP-3 was observed in human normal TM and in the inner wall of Schlemm's canal. In general, immunoreactions for all of the tested MMPs were more intense in POAG samples than in ExG samples or in the control group. The only exception was the MMP-2 level, which was the highest in the control group. The staining intensity of MMP-1 or MMP-3 was significantly higher in POAG when compared to ExG. TIMP-1 was significantly increased in POAG compared with ExG and there were no marked differences in the levels of TIMP-2 or TIMP-3 between POAG and ExG. The ratios of MMP-1/TIMP-1 and MMP(1+2+3+9) and TIMP(1+2+3) were significantly higher in samples from POAG compared to those of ExG. CONCLUSIONS: Our results reveal an expression imbalance between MMPs and their endogenous tissue inhibitors in tissue samples from patients with POAG and ExG. Differences in immunohistochemical reactions reflect discrete local pathogenic mechanisms involved in POAG and ExG. With respect to the proposed role of MMPs in the remodeling of ECM material, this may point to a weaker reactivity to the accumulation of ECM material in TM in ExG than POAG eyes.
BACKGROUND: The aim of the study was to evaluate the vitreous penetration of two commercially available ophthalmic fluoroquinolones: ofloxacin and levofloxacin. METHODS: This prospective, double-blind, randomized clinical trial comprised 16 patients scheduled for vitrectomy surgery of one eye for macular hole or macular pucker. The patients were randomly assigned to receive topical ofloxacin 0.3% (n=9) or levofloxacin 0.5% (n=7) the day before, one drop at noon, 4 p.m., 8 p.m. and midnight. The next morning, patients were given their assigned masked antibiotic every 5 min for four doses starting 1 h before surgery. The vitreous humour samples, at least 0.3 ml each, were collected 1 h after the administration of the last dose, at the beginning of the pars plana vitrectomy with infusion disconnected. Samples were assayed for ofloxacin and levofloxacin concentrations by a method using high-performance liquid chromatography (HPLC) coupled with single mass spectrometry with electrospray ionization RESULTS: Equal topical administration of levofloxacin yielded 2.5 times higher vitreal concentration than ofloxacin. The mean vitreous concentrations of ofloxacin and levofloxacin were 5.30+/-3.04 (SD) ng/ml and 13.09+/-5.24 ng/ml, respectively (P=0.002). CONCLUSIONS: Equal dosing with topical administration of levofloxacin 0.5% and ofloxacin 0.3% allows better penetration into the vitreous for levofloxacin, but the levels of mean concentrations of each drug did not exceed the MIC(90) or MIC(50) for most ocular pathogenic bacteria in terms of conventional endophthalmitis therapy.
PURPOSE: To retrospectively compare the efficacy of deep sclerectomy in the treatment of primary open-angle glaucoma (POAG) and exfoliation glaucoma (ExG). METHODS: Deep sclerectomy with either collagen or hyaluronate implants was performed in 31 eyes (45%) with POAG and 38 eyes (55%) with ExG. Pre- and postoperative intraocular pressure (IOP) was recorded, as was the number of glaucoma medications used pre- and postoperatively in each group. The follow-up data referred to a mean period of 18 months (range: 2 weeks to 36 months). RESULTS: At 18 months, complete success had been achieved in 56.3% of POAG eyes and 44.9% of ExG eyes. Qualified success had been achieved in 83.1% and 71.6% of POAG and ExG eyes, respectively. The mean IOP was 18.6 mmHg in POAG eyes and 16.3 mmHg in ExG eyes. YAG-descemetotomies were performed in nine eyes in each group. There were no statistically significant differences between the groups in IOP (except at 1 week postoperatively in favour of POAG; p = 0.05), success rates, need for postoperative glaucoma medication or number of complications. Reoperations were required in three (10%) POAG eyes and seven (18%) ExG eyes. CONCLUSIONS: Deep sclerectomy is equally effective in controlling IOP in both POAG and ExG and has low rates of serious complications, even when the surgeon is inexperienced in the technique. Both survival rates and IOP control were similar between the groups, and there were no serious intra- or postoperative complications.
Development of age-related macular degeneration (AMD) is associated with functional abnormalities and cell death in retinal pigment epithelial (RPE) cells attributable to oxidative stress. To minimize the adverse effects of oxidative stress, cells activate their defence systems, e.g., via increased expression of heat shock protein (Hsp), activation of stress sensitive AP-1 and NF-kappaB transcription factors. In this study, we examined the accumulation of Hsp70 protein, activation of AP-1 and NF-kappaB transcription factors in human ARPE-19 cells subjected to a 4-hydroxynonenal (HNE)-induced oxidative stress. In addition, the influence of Hsp90 inhibitor geldanamycin (GA) was studied in HNE-treated cells. Mitochondrial metabolic activity and apoptosis were determined to evaluate cell death in the ARPE-19 cells. The ARPE-19 cells showed increased accumulation of Hsp70 protein before of the cytotoxic hallmarks appearing in response to HNE. In contrast, increased DNA-binding activities of AP-1 or NF-kappaB transcription factors were not seen under HNE insults. Interestingly, GA significantly increased cell death in the HNE-treated cells, which was involved in caspase-3 independent apoptosis. This study reveals that the Hsps have an important role in the cytoprotection of RPE cells subjected to HNE-derived oxidative stress.
Reversible protein phosphorylation regulates the biological activities of many human proteins involved in crucial cellular processes, e.g., protein-protein interactions, cell signaling, gene transcription, cell growth, and death. A malfunction of cellular homeostasis in retinal pigment epithelial (RPE) cells is involved in the age-related retinal degeneration. In this study, we examined cytotoxicity in human RPE cells subjected to the protein phosphatase inhibitor, okadaic acid (OA). Moreover, the influence of Hsp90 inhibitor geldanamycin (GA), a benzoquinone ansamycin, in cytoprotection was assessed. Hsp70 protein levels were analyzed by Western blot. Cellular viability was determined by LDH and MTT assays. To study apoptotic cell death, caspase-3 enzyme activity was measured by assaying the cleavage of a fluorescent peptide substrate and Hoechst dye was used to visualize nuclear morphology. OA treatment caused morphological changes and induced cytotoxicity by caspase-3-independent manner in the RPE cells. No evidence of nuclear fragmentation was observed in response to OA. Interestingly, GA treatment accumulated Hsp70 protein and attenuated OA-induced cytotoxicity. This study suggests that Hsp70 and Hsp90 are closely related to cytoprotection of RPE cells in response to protein phosphatase inhibition.
BACKGROUND: Recent studies have suggested that the relationship between elevated plasma homocysteine (Hcy) and increased risk of vascular disease holds also for certain diseases of the eye with vascular aetiology. Elevated plasma Hcy levels have been noted among patients with exfoliation syndrome (XFS). The purpose of this study was to establish whether subjects with XFS have higher plasma and aqueous humour Hcy levels values than non-XFS subjects, particularly in relation to vitamin B status. METHODS: Using a cross-sectional study design, 36 subjects with XFS and 36 non-XFS subjects with intraocular pressure (IOP) lower than 23 mmHg, matched by age and gender, were first selected. The participant exclusion criteria included parameters known to alter Hcy metabolism. In the XFS group, 11 subjects had a concurrent diagnosis of exfoliative glaucoma (XFG). Fasting plasma and aqueous humour Hcy samples were collected, along with erythrocyte folate (E-Fol) and serum vitamin B6 and B12 samples. The Hcy samples were analysed using a fluorescence polarization immunoassay method. RESULTS: Plasma Hcy level was significantly higher (P=0.020, after Bonferroni correction for multiple testing) in the XFS group than in the controls. The Hcy concentrations in the aqueous humour did not differ statistically between the two groups. Plasma and aqueous humour Hcy concentrations were not statistically significantly correlated within the groups of exfoliation-positive and -negative subjects. E-Fol, and serum vitamin B6 and B 12 levels did not differ statistically between the XFS group and the control group. CONCLUSIONS: The finding that subjects with XFS are more prone to elevated plasma Hcy emphasizes exfoliation as a clinical sign and a marker of thromboembolic vasculopathies induced by hyperhomocysteinaemia.
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PURPOSE: Cross-sectional analysis of iris transluminance in type 2 diabetic patients compared with control subjects, all followed in a cohort study. METHODS: A cohort consisting of a well-characterized group of 82 type 2 diabetic patients were followed for 10 years after diagnosis, as were 125 control subjects. The prevalence of iris transluminance was determined by transscleral transillumination and by grading of black-and-white positive prints at the 10-year examination. The frequency of diabetic retinopathy was prospectively determined by grading of fundus photographs at baseline and after five and 10 years. RESULTS: Iris transluminance was found in 27% of diabetic patients and 8.0% of control subjects (P = 0.001). The diabetic patients with more severe and short-term retinopathy more commonly had abnormal iris transluminance than those with no or only mild retinopathy (P < 0.05). Iris transluminance was not associated with intraocular pressure or glycemic control. CONCLUSIONS: In type 2 diabetic patients, abnormal iris transluminance tended to associate with more severe and short-term retinopathy. Therefore we assume that hypoxia is responsible for the defects in the pigment layer of the iris. Thus, abnormal iris transluminance may serve as a marker for rapidly progressive retinopathy.
BACKGROUND: Endoscopic dacryocystorhinostomy (EN-DCR) is increasing in popularity as a treatment of nasolacrimal obstructions because it has proven to be an effective and safe procedure. In this study the success of EN-DCR combined with or without bicanalicular silicone stents was evaluated in patients with nasolacrimal obstructions. METHODS: Forty-two consecutive EN-DCR procedures were performed in 36 patients during 2000-2004. The surgery was primary in 23 cases and revision in 19 cases. Bicanalicular silicone stents were inserted in 18 cases and in 24 cases stenting was avoided. RESULTS: The overall success rate after EN-DCR was 81%. The success rate of EN-DCR was 89% with silicone tubing and 75% without silicone tubing. The mean duration of postoperative follow-up was 4 months. CONCLUSION: In our retrospective study no significant statistical differences were seen between the patients with stenting compared with patients without stenting. However, prospective, randomized studies are clearly needed to answer the question of whether the use of stents is advisable.