Abstract
This study investigated the effects of omidenepag (OMD), a novel selective EP2 receptor agonist, on human trabecular meshwork (HTM) cells, monkey Schlemm’s canal endothelial (SCE) cells, and ...porcine ciliary muscle (CM) to clarify the mechanism of intraocular pressure (IOP) reduction involving conventional outflow pathway. In HTM and SCE cells, the effects of OMD on transforming growth factor-β2 (TGF-β2)-induced changes were examined. The expression of actin cytoskeleton and extracellular matrix (ECM) proteins, myosin light chain (MLC) phosphorylation in HTM cells were evaluated using real-time quantitative PCR, immunocytochemistry, and western blotting. The expression of barrier-related proteins, ZO-1 and β-catenin, and permeability of SCE cells were evaluated using immunocytochemistry and transendothelial electrical resistance. The CM contraction was determined by contractibility assay. OMD significantly inhibited expression of TGF-β2 induced mRNA, protein, and MLC-phosphorylation on cytoskeletal and ECM remodeling in the HTM dose dependently. In SCE cells, OMD suppressed TGF-β2-induced expression of the barrier-related proteins and decreased SCE monolayer permeability. OMD at 3 µM significantly inhibited CM contraction, however, the effect was not significant at lower concentrations. IOP lowering effect of OMD through conventional outflow pathway is exerted by increasing outflow facilities with the modulation of TM cell fibrosis and SCE cell permeability.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
To evaluate the effectiveness of MicroPulse
®
transscleral laser therapy (MP-TLT) using both the original and revised MicroPulse P3
®
delivery probes in patients with refractory glaucoma.
...Study design
Retrospective study
Methods
We analyzed the data of patients with refractory glaucoma who underwent MP-TLT with the original and with the revised MicroPulse P3
®
Delivery Device from January 2018 to December 2020 at the University of Tokyo Hospital and who were followed up for 3 months. Patients’ demographics, preoperative and postoperative intraocular pressure (IOP), medication scores, best-corrected visual acuity (BCVA), and complications were analyzed.
Results
This study enrolled 40 patients in both probe groups. At baseline, the mean IOP was 31.1 mmHg in the original group and 29.2 mmHg in the revised group, and it decreased to 22.6 mmHg and 21.6 mmHg after 3 months, respectively (paired t-test p=0.001, 0.001). No significant difference was noted between the number of medications and BCVA at baseline and 3 months in either probe group (paired t-test, p>0.05). Nor were any serious complications observed.
Conclusion
MP-TLT using the revised MicroPulse P3
®
Delivery Device for the treatment of refractory glaucoma was effective in reducing IOP across glaucoma types with an excellent safety profile and was well-tolerated by the patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
To evaluate the long-term safety and effectiveness of the Preserflo MicroShunt in Japanese primary open-angle glaucoma (POAG) patients.
Study design
Single-site, nonrandomized observational ...study.
Patients and methods
Eight eyes of 7 POAG patients were included. The surgical complications and interventions were monitored. The preoperative and postoperative intraocular pressures (IOPs), numbers of antiglaucoma medications, logarithm of the minimum angle of resolution visual acuity (VA), mean deviation (MD) slope, and corneal endothelial cell density (CECD) were compared retrospectively.
Results
The mean follow-up period was 68.9 months (range, 48–76 months). The baseline IOP of 17.9 ± 3.5 mmHg and the number of glaucoma medications of 3.5 ± 0.5 were significantly reduced at subsequent follow-up visits. At 1, 2, 3, 4, 5, and 6 years postoperatively, the IOPs were 13.8 ± 2.9, 12.8 ± 2.3, 12.1 ± 3.2, 12.6 ± 2.5, 12.3 ± 1.0, and 13.5 ± 3.1 mmHg, respectively, with the use of 1.6 ± 1.4, 1.6 ± 1.6, 1.5 ± 1.4, 1.5 ± 1.4, 1.9 ± 1.3, and 2.0 ± 1.1 medications. Postoperative transient hyphema occurred in 1 eye. Postoperative needling was required in 5 eyes, 12 times in total. No eyes showed significant VA decline, except for 1 eye with a severe central visual field defect that existed preoperatively. The preoperative MD slope of − 1.6 ± 1.2 dB/year improved significantly, to − 0.3 ± 0.2 dB/year (
P
= 0.023), postoperatively. The baseline CECD decreased from 2595 ± 292 to 2478.4 ± 255 postoperatively.
Conclusion
The microshunt surgical procedure is safe and effective for Japanese POAG patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
To examine the effect of switching from a prostanoid FP receptor agonists to EP2 receptor agonist (omidenepag isopropyl) on the deepening of the upper eyelid sulcus (DUES) and intraocular ...pressure (IOP) in Japanese glaucoma patients over 3 months post treatment.
Study design
Prospective observational study.
Methods
Patients with glaucoma who received FP receptor agonists treatment and had complained of DUES-related reduction in quality of life were included. Their FP receptor agonists was switched to omidenepag isopropyl without a drug holiday. At baseline and 1 and 3 months post-switch, photographs were taken and the changes in DUES were assessed by three independent observers. IOP and adverse events were also assessed.
Results
The study included 23 eyes of 23 patients (6 men, 17 women; average age, 60.6 years). After switching, DUES improved in 12 eyes at 1 month and in 16 eyes at 3 months; eyes in the remaining patients showed no worsening of the condition. The mean IOP before switching was 15.3 ± 3.3 mmHg (95% confidence interval 13.9–16.7 mmHg). Following the switch, the mean IOP values were 15.6 ± 3.3 mmHg (14.1–17.0 mmHg) at 1 month and 15.5 ± 3.3 mmHg (14.1–16.9 mmHg) at 3 months (P = 1.0 at 1 month, P = 1.0 at 3 months; both adjusted by Bonferroni correction). No adverse effects were observed.
Conclusion
Omidenepag isopropyl improved DUES while maintaining IOP in over 70% of Japanese patients with glaucoma who exhibited DUES caused by FP receptor agonists; the improvement was observed within 3 months after switching from FP receptor agonists.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
To compare 12-month clinical results of spatula-shaped and dual-blade microhooks
ab interno
trabeculotomy with phacoemulsification.
Study design
Retrospective comparative study.
Methods
We ...conducted a retrospective chart review of Japanese open-angle glaucoma patients who underwent
ab interno
trabeculotomy with phacoemulsification with a 12-month follow-up. Two types of trabecular hook were used: the spatula-shaped Tanito Trabeculotomy
ab interno
Micro-hook
®
and the Kahook Dual Blade
®
. Changes in intraocular pressure (IOP) and medication scores comprised the main outcome metrics. We also analyzed and compared patient demographics and the occurrence of complications.
Results
Trabeculotomy was performed using a spatula-shaped hook in 17 eyes and a dual-blade hook in 15 eyes. Significant reductions in IOP (
p
< 0.001) and medication scores (
p
< 0.001) were noted in both groups after the 1-month time point. The percentage changes of IOP from baseline at each time point were not significantly different between groups, though there was a significant difference in medication scores at 12 months (
p
= 0.0192). Postoperative complications occurred similarly in both groups; one case in the dual-blade group required additional filtration surgery.
Conclusions
Ab interno
trabeculotomy with phacoemulsification was effective in lowering IOP both with spatula-shaped and with double-blade microhooks. At 12 months more medications were used postoperatively in the spatula-shaped microhook group; however, the reductions in the medication scores from baseline were statistically significant in both groups.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This study aimed to evaluate the diagnostic ability and sectoral structure function relationship of circumpapillary vessel density (cpVD) and macular vessel density (mVD) with optical coherence ...tomography angiography (OCTA) in early glaucomatous (EG) eyes. 224 EG eyes of 167 patients (mean deviation (MD) > - 6 dB) and 70 normal eyes of 70 subjects were enrolled in this retrospective cross-sectional study. All patients underwent OCT and OCTA scanning. Diagnostic abilities were evaluated with area under receiver operating characteristic curves (AUROC). Structure function relationships of superior, inferior and Garway-Heath sectoral values with its corresponding visual field (VF) sensitivity were determined using linear mixed models. AUROCs were 0.798, 0.621, 0.876 and 0.835 for cpVD, mVD, circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and ganglion cell-inner plexiform layer, respectively. AUROC of cpVD was significantly lower than cpRNFLT (P = 0.010) and higher than mVD (P < 0.001). All Garway-Heath sectors of cpVD significantly correlated with its corresponding VF sensitivity except for the nasal sector. MVD also showed significant structure function relationship and the correlations were stronger in the perifoveal region (6 mm annulus) than in the parafoveal region (3 mm annulus). CpVD demonstrated moderate diagnostic ability and both cpVD and mVD demonstrated significant association with VF sensitivity in EG eyes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
To investigate the outcomes of fornix-based trabeculectomy in Japanese patients with glaucoma based on more than five years of preoperative data.
Study design
Retrospective case series
...Methods
This study consisted of 35 eyes of 35 Japanese glaucoma patients (mean age: 60.6, standard deviation (SD) 11.5 years) who received initial fornix-based trabeculectomy from a single ophthalmology clinic, with one or more reliable visual field test results per year from at least five years before and after the surgery. Measurements included postoperative mean intraocular pressure (IOP), standard deviation of IOP, medication scores, mean deviation slope, and total deviation slope were evaluated based on preoperative data. The relationship between mean IOP, SD-IOP and the visual field (VF) deterioration speed was also analysed.
Results
The mean follow-up period before surgery was 6.15 (SD 0.97) years and post surgery it was 5.95 (SD 0.63) years. The preoperative mean IOP of 14.6 (SD 2.3) mmHg significantly decreased to 9.2 (SD 2.2) mmHg (
P
<.001). The preoperative medication score 2.7 (SD 0.5) significantly decreased to 0.1 (SD 0.4,
P
<.001). The preoperative MD slope of −0.52 (SE 0.047) dB/year significantly improved to −0.31 (SE 0.14) dB/year (
P
<.01), with improvement in the superior hemifield (
P
≤.018). Inferior hemifield (
P
>.10) did not follow the trend. Neither mean IOP nor SD-IOP correlated with the VF deterioration speed.
Conclusions
Fornix-based trabeculectomy is an acceptable procedure for initial surgical management of glaucoma, especially for maintenance of superior VF.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Trabecular meshwork constitutes the conventional outflow pathway and controls intraocular pressure by regulating aqueous outflow. Mechanical stimulation has been studied as one of the triggers to ...regulate aqueous outflow in trabecular meshwork, but it is not well understood. We investigated that how transient receptor potential cation channel subfamily V member 4 (TRPV4) functions in human trabecular meshwork cells (HTMC) and affects intraocular pressure (IOP). HTMC were treated with TRPV4 siRNA, followed by incubation for 24 hours. We confirmed the suppression of TRPV4 mRNA expression and the reduction of Ca.sup.2+ influx by the TRPV4 agonist GSK1016790A in TRPV4 siRNA-treated HTMC. TRPV4 siRNA-treated HTMC exhibited a significant reduction in Ca.sup.2+ influx and production of arachidonic acid and prostaglandin (PG) E.sub.2 induced by mechanical stretch, and direct activation of TRPV4 by GSK1016790A increased production of arachidonic acid, PGE.sub.2, and PGD.sub.2 and inhibited gel contraction. Furthermore, TRPV4-deficient mice had higher IOP than wild-type mice, and GSK1016790A administration lowered IOP. These results suggest that TRPV4 mediates the cellular response induced by trabecular meshwork stretch, leading to IOP reduction through the production of prostaglandins and inhibition of cell contraction. Targeting TRPV4 may have therapeutic benefits that lead to lowering IOP in glaucoma patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
To evaluate omidenepag isopropyl (OMDI) for its efficacy in intraocular pressure control (IOP) and adverse reactions following administrations in Japanese patients with open-angle glaucoma ...(OAG) over a 3-month period.
Study design
Retrospective observational study.
Subjects and methods
Group 1 included untreated OAG patients, Group 2 included OAG patients treated with prostaglandin F (FP) receptor agonists (monotherapy) and Group 3 included OAG patients treated with multidrug therapy, including FP receptor agonists. OMDI was newly administered in Group 1, and FP receptor agonists were switched to OMDI in Group 2. In Group 3, all other ocular hypotensive medications were continued except FP receptor agonists. IOP changes were examined, and adverse reactions were retrieved from the medical records.
Results
Group 1 included 32 eyes, Group 2, 20 eyes and Group 3, 17 eyes. In Group 1, the baseline IOP was 15.7 mmHg (95% confidence interval CI 14.7–16.8 mmHg). After eyedrop treatment, the IOP was 14.1 mmHg (P < 0.001) at 1 month and 13.7 mmHg (P < 0.001) at 3 months. By contrast, in Group 2 and Group 3, switching FP receptor agonists to OMDI did not result in significant IOP changes (P ≥ 0.71). Six patients developed adverse reactions (hyperemia, headache, ocular pain, and swollen eyelids).
Conclusions
New administration of OMDI significantly reduced the IOP. Furthermore, the IOP did not change after switching from FP receptor agonists to OMDI, including multidrug therapy. OMDI can be used as a first-line drug and is comparable to FP receptor agonists in Japanese patients with OAG.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Trabecular meshwork constitutes the conventional outflow pathway and controls intraocular pressure by regulating aqueous outflow. Mechanical stimulation has been studied as one of the triggers to ...regulate aqueous outflow in trabecular meshwork, but it is not well understood. We investigated that how transient receptor potential cation channel subfamily V member 4 (TRPV4) functions in human trabecular meshwork cells (HTMC) and affects intraocular pressure (IOP). HTMC were treated with TRPV4 siRNA, followed by incubation for 24 hours. We confirmed the suppression of TRPV4 mRNA expression and the reduction of Ca2+ influx by the TRPV4 agonist GSK1016790A in TRPV4 siRNA-treated HTMC. TRPV4 siRNA-treated HTMC exhibited a significant reduction in Ca2+ influx and production of arachidonic acid and prostaglandin (PG) E2 induced by mechanical stretch, and direct activation of TRPV4 by GSK1016790A increased production of arachidonic acid, PGE2, and PGD2 and inhibited gel contraction. Furthermore, TRPV4-deficient mice had higher IOP than wild-type mice, and GSK1016790A administration lowered IOP. These results suggest that TRPV4 mediates the cellular response induced by trabecular meshwork stretch, leading to IOP reduction through the production of prostaglandins and inhibition of cell contraction. Targeting TRPV4 may have therapeutic benefits that lead to lowering IOP in glaucoma patients.
Full text
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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