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PurposeTo investigate the effects of laser suture lysis (LSL) on filtration openings after trabeculectomy.MethodsProspective study analyzing the changes in the location and width of filtration openings, fluid cavity height, total bleb height, bleb wall thickness, and bleb wall intensity before and after LSL using three-dimensional anterior segment optical coherence tomography (3D AS-OCT).ResultsFourteen patients had clear scleral flap image analysis. As five patients underwent LSL twice and two patients underwent LSL thrice, 23 comparison studies were possible. After LSL the intraocular pressure (IOP) decreased (P=0.0015) from 20.5±5.3 to 14.9±6.4 mm Hg, and the fluid cavity height increased significantly from 0.2±0.2 mm to 0.3±0.1 mm (P=0.0094). Other bleb parameters were not significantly different when comparing before and after LSL. When the IOP reduction ratio was >25% following LSL, the width of the filtration openings on the LSL side, the total bleb height, and the fluid cavity height increased (P=0.0273, 0.0342, and 0.0024, respectively). In multiple regression analysis the changes in fluid cavity height, the wall thickness, the wall intensity, and the width of the filtration opening were positively associated with the IOP reduction rate (P=0.0428, 0.0226, 0.0420, and 0.0356, respectively).Conclusions3D AS-OCT allowed a detailed examination of the internal morphology of filtration blebs and openings before and after LSL. The changes in the internal morphology were closely associated with the success of LSL to decrease IOP. [ABSTRACT FROM AUTHOR]

The caveolin 1 to caveolin 2 (CAV1-CAV2) gene region on chromosome 7q31 has been reported to be associated with susceptibility to primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) in previous studies. We investigated whether genetic variants in the CAV1-CAV2 region are associated with NTG in Japanese patients. Two hundred and ninety-two Japanese patients with NTG and 352 Japanese healthy controls were recruited. We genotyped three single-nucleotide polymorphisms; that is, rs1052990, rs4236601, and rs7795356, in the CAV1-CAV2 gene region and assessed the allelic diversity among cases and controls. The frequency of the minor allele (G) of rs1052990 was significantly decreased in NTG cases compared with controls (P=0.014, OR=0.71), whereas NTG or POAG cases had a significantly higher frequency of the allele than controls in previous studies. Conversely, rs7795356 did not show any significant association with NTG cases, and rs4236601 was monomorphic in the Japanese study population. Our findings did not correspond with previous positive results, suggesting that CAV1-CAV2 variants studied in the present study are not important risk factors for NTG susceptibility in all populations. Further studies are needed to elucidate the possible contribution of the CAV1-CAV2 region to the development of glaucoma. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate the association between normal tension glaucoma and the candidate disease locus glaucoma 1, open angle, B (GLC1B) on chromosome 2. There are many reports describing the results of association or linkage studies for primary open angle glaucoma (POAG), with GLC1B as one of the loci associated with normal or moderately elevated intraocular pressure. However, there are few reports about the association of genes or defined genomic regions with normal tension glaucoma, which is the leading type of glaucoma in Japan. The GLC1B locus is hypothesized to be a causative region for normal tension glaucoma. Methods: Genomic DNA was extracted from whole blood of normal tension glaucoma (n = 143) and healthy controls (n = 103) of Japanese origin. Results: Fifteen microsatellite markers within and/or near to the GLC1 B locus were genotyped, and their association with normal tension glaucoma was analysed. Two markers D2S2264 and D2S176 had significant positive associations. Conclusion: The D2S176 marker had the strongest significant association and it is located 24 kb from the nearest gene NCK2, which now becomes an important new candidate gene for future studies of its association with normal tension glaucoma. [ABSTRACT FROM AUTHOR]

Familial amyloidotic polyneuropathy (FAP) is the common form of hereditary generalized amyloidosis and is characterized by the accumulation of amyloid fibrils in the peripheral nerves and other organs. Liver transplantation has been utilized as a therapy for FAP, because the variant transthyretin (TTR) is predominantly synthesized by the liver, but this therapy is associated with several problems. Thus, we need to develop a new treatment that prevents the production of the variant TTR in the liver. In this study, we used HepG2 cells to show in vitro conversion of the TTR gene by single-stranded oligonucleotides (SSOs), embedded in atelocollagen, designed to promote endogenous repair of genomic DNA. For the in vivo portion of the study, we used liver from transgenic mice whose intrinsic wild-type TTR gene was replaced by the murine TTR Val30Met gene. The level of gene conversion was determined by real-time RCR combined with mutant-allele-specific amplification. Our results indicated that the level of gene conversion was approximately 11 and 9% of the total TTR gene in HepG2 cells and liver from transgenic mice, respectively. Gene therapy via this method may therefore be a promising alternative to liver transplantation for treatment of FAP. [ABSTRACT FROM AUTHOR]

Objective: To characterize the pharmacokinetics and pharmacodynamics of acetazolamide in patients with transient intraocular pressure (IOP) elevation and to provide individual patients with the optimal dosage regimen for this drug. Methods: We studied 17 patients with transient IOP elevation, who were given 62.5–500 mg acetazolamide orally as single or repetitive doses. Plasma acetazolamide concentration and IOP were measured at approximately 1, 3, 5, and 9 h after the last acetazolamide administration. Pharmacokinetics and pharmacodynamics were analyzed by nonlinear mixed-effect modeling using the program NONMEM. Results: The plasma concentration profile of acetazolamide was characterized by a one-compartment model with first-order absorption. The apparent oral clearance was related to the creatine clearance (CCR) which was estimated by the Cockcroft and Gault equation, as follows: 0.0468 · CCR l · h−1. The estimated apparent oral volume of distribution, first-order absorption rate constant, and absorption lag time were 0.231 l · kg−1, 0.821 · h−1, and 0.497 h, respectively. IOP after oral acetazolamide administration was characterized by an Emax model. The maximal effect in lowering the IOP (Emax) was 7.2 mmHg, and the concentration corresponding to 50% of the maximal effect (EC50) was 1.64 μg · ml−1. As 70% of Emax was achieved at a plasma concentration of 4 μg · ml−1, this concentration was considered satisfactory for lowering IOP. The recommended dosage was calculated so that the minimum plasma concentration at steady state exceeded this target concentration; 250 mg t.i.d., 125 mg t.i.d., 125 mg b.i.d., and 125 mg once daily for the patients with CCR values of 70, 50, 30, and 10 ml · min−1, respectively. Conclusion: Measuring plasma concentrations of acetazolamide and subsequent pharmacokinetic and pharmacodynamic analyses are useful for estimating its concentration-dependent effectiveness in lowering the IOP in individual patients. The dosage regimen presented in this study is expected to improve the benefits of acetazolamide pharmacotherapy in most elderly patients with transient rises in IOP following intraocular surgery. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to evaluate the safety and effectiveness of trans-Tenons retrobulbar triamcinolone acetonide (TA) injection for macular oedema associated with branch retinal vein occlusion (BRVO). Methods: We reviewed the medical records of 50 consecutive patients with macular oedema associated with BRVO who were treated with trans-Tenon's retrobulbar TA injection (20 mg) as initial treatment for a follow-up period of at least 12 months. Foveal thickness determined by optical coherence tomography, visual acuity, intraocular pressure (lOP) and cataract progression were measured. Results: The mean duration between oedema onset and TA injection was 4.9 months. Foveal thickness decreased significantly at 3 months after injection (p<0.0001). Furthermore, the percentage reduction in foveal thickness in eyes with posterior vitreous detachment (PVD; n = 23) was significantly greater than that without PVD (n = 27, p = 0.003L Improved visual acuity by at least 0.20 log minimum angle of resolution (IogMAR) was seen in 22 eyes (44%; 11 eyes with PVD and 11 eyes without PVD). After completion of the 3-month follow-up, 29 eyes (58%) needed additional treatment including TA injections or pars plana vitrectomy (PPV). PPV seemed to be effective for macular oedema resistant to TA. lop elevation and cataract progression occurred in less than 10% of all patients. Conclusions: Trans-Tenon's retrobulbar TA injection appeared safe and relatively effective for macular oedema associated with BRVO. In eyes resistant to TA injection, PPV may be effective as an adjunctive treatment. [ABSTRACT FROM AUTHOR]

Aim: To investigate the phenotypes associated with cytochrome P4501B1 gene (CYP1B1) mutations in Japanese patients with primary congenital glaucoma (PCG). Methods: 66 Japanese patients with PCG were screened for sequence mutations in the CYP1B1 gene using single strand conformation polymorphism analysis followed by automated DNA sequencing. 11 cases had a CYP1B1 mutation in both alleles (the mutation group) and 21 cases did not have a CYP1B1 mutation (the "no mutation" group). The clinical features, such as age of onset, sex, intraocular pressure, and Descemet's membrane rupture, of the two groups were compared. Results: The clinical symptoms and signs did not differ for the two groups. The mean age at onset was 1.7 months in the mutation group and 3.1 months in the no mutation group, and the male:female ratio was 6:5 in the mutation group and 19:2 in the no mutation group. Both of these differences were statistically significant. Conclusions: In clinically diagnosed cases of PCG, a subgroup shows a CYP1B1 gene mutation. Age at onset was earlier in PCG patients with CYP1B1 mutations than in patients without mutations. Women were more prevalent among patients with mutations than those without mutations. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented that describes two cases of ocular decompression retinopathy following traculectomy with mitomycin C associated with familial amyloidotic polyneuropathy in two female patients.