The gonio scratch study: methodology of a multicenter clinical trial establishing a new minimally invasive glaucoma surgery.

There are numerous surgical procedures for glaucoma. Minimally invasive glaucoma surgery is becoming popular; however, the disadvantage is the high incidence of anterior chamber hemorrhage. Heavy bleeding can also lead to increased intraocular pressure (IOP) postoperatively. Gonio scratch is a surgical procedure that improves aqueous humor outflow by rubbing off deposits on the trabecular meshwork with a Diamond Dusted Sweeper. As the conjunctiva and trabecular meshwork are not incised, no postoperative bleeding is expected, and the IOP spike will be minimal. We designed this study to determine the efficacy and safety of gonio scratch. This is an on-going multicenter, prospective, clinical trial. Patients who are scheduled for glaucoma surgery with or without cataract surgery are being enrolled. A total of 80 eyes will be recruited in the Hiroshima University Hospital, Miyoshi Eye Clinic, Yokoyama Retina Clinic, and Kusatsu Eye Clinic. All patients will undergo gonio scratch. When combined with cataract surgery, gonio scratch is performed after the intraocular lens is inserted. The primary study endpoint is the change in IOP from baseline to 1 year after surgery. The secondary endpoints are complications, number of glaucoma medications, surgical time, and changes in visual acuity and the visual field. This study protocol was approved by the institutional review board of Hiroshima University. The trial results will be shared with the scientific community at international conferences and by publication in a peer-reviewed journal. Trial registration number is jRCTs062200003.

Ex-PRESS Implantation versus Trabeculectomy for Long-Term Maintenance in Patients with Open-Angle Glaucoma.

Purpose: To compare the efficacy of Ex-PRESS implantation (EXP) with that of trabeculectomy (TLE) with mitomycin C for maintaining low target intraocular pressure (IOP) in patients with open-angle glaucoma. Patients and Methods: Patients were randomly assigned to receive EXP or TLE. Surgical success was defined according to three target mean IOP ranges (5 mmHg ≤ IOP ≤ 18 mmHg [criterion A], 5 mmHg ≤ IOP ≤ 15 mmHg [criterion B], and 5 mmHg ≤ IOP ≤ 12 mmHg [criterion C]) representing reductions of at least 20% below the baseline on two consecutive follow-up visits 3 months post-surgery, with or without antiglaucoma medication and without further glaucoma surgery. Participants were divided into three subgroups based on baseline mean deviation (MD) values: early (MD ≥ -6 dB), moderate (-6 dB > MD ≥ -12 dB), and advanced (-12 dB > MD). Survival rates were calculated by subgroup. Results: A total of 73 patients, including 30 in the EXP group and 43 in the TLE group, were included in the study. No significant differences in baseline ocular or demographic characteristics were found between the two groups. No significant difference in IOP was noted every 6 months. After the 3-year follow-up, success rates were A) 60.0% and 60.2%, B) 45.7% and 58.1%, and C) 31.5% and 40.5% for the EXP and TLE groups, respectively. Moreover, there was no difference in success rate based on glaucoma level. Many glaucoma medications administered before surgery were associated with a higher failure rate in the TLE group but not in the EXP group. Conclusion: Both procedures resulted in similar IOP reductions and success rates for a low target IOP. The number of preoperative glaucoma medications was a risk factor for TLE failure.

Loss of PWT7, Located on a Supernumerary Chromosome, Is Associated with Parasitic Specialization of Pyricularia oryzae on Wheat.

Pyricularia oryzae, a blast fungus of gramineous plants, is composed of various host genus-specific pathotypes. The avirulence of an Avena isolate on wheat is conditioned by PWT3 and PWT4. We isolated the third avirulence gene from the Avena isolate and designated it as PWT7. PWT7 was effective as an avirulence gene only at the seedling stage or on leaves. PWT7 homologs were widely distributed in a subpopulation of the Eleusine pathotype and the Lolium pathotype but completely absent in the Triticum pathotype (the wheat blast fungus). The PWT7 homolog found in the Eleusine pathotype was one of the five genes involved in its avirulence on wheat. A comparative analysis of distribution of PWT7 and the other two genes previously identified in the Eleusine pathotype suggested that, in the course of parasitic specialization toward the wheat blast fungus, a common ancestor of the Eleusine, Lolium, Avena, and Triticum pathotypes first lost PWT6, secondly PWT7, and, finally, the function of PWT3. PWT7 or its homologs were located on core chromosomes in Setaria and Eleusine isolates but on supernumerary chromosomes in Lolium and Avena isolates. This is an example of interchromosomal translocations of effector genes between core and supernumerary chromosomes. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

A multicenter phase II study on the safety of rho-kinase inhibitor (ripasudil) with needling for the patients after trabeculectomy.

Background: There is no established method of maintaining or reducing intra ocular pressure after the needling procedure for failing blebs post trabeculectomy. Regarding newer antihypertensive medications, ripasudil, which is a rho-associated protein kinase inhibitor ophthalmic solution, was able to prevent excessive scarring in vitro. This study aims to evaluate the safety of glaucoma patients submitted to the needling procedure and administered ripasudil for preventing scarring after the procedure. We also investigate the efficacy of ripasudil after needling for bleb failure through suppression of fibrosis to the bleb. Methods: This study is a multicenter, open-label, single-arm, phase II trial to evaluate the safety and efficacy of ripasudil in glaucoma patients after the needling procedure. Forty patients who will undergo needling at least 3 months after trabeculectomy will be recruited in Hiroshima university hospital and Hiroshima eye clinic. All the patients will instill ripasudil two times per day for three months after the needling procedure. The primary endpoint is the safety of ripasudil. Conclusions: We plan to establish the safety of ripasudil and to collect information involving the efficacy of ripasudil widely in this study.

Effects of Ripasudil, a Rho-Kinase Inhibitor, on Scar Formation in a Mouse Model of Filtration Surgery.

PURPOSE: Glaucoma is a leading cause of blindness worldwide. Characteristic changes occur in the optic nerve and visual field of patients with glaucoma; optic nerve damage can be mitigated by lowering intraocular pressure. Treatment modalities include drugs and lasers; filtration surgery is necessary for patients with insufficient intraocular pressure reduction. Scar formation often contributes to glaucoma filtration surgery failure by increasing fibroblast proliferation and activation. Here, we examined the effects of ripasudil, a Rho-associated protein kinase (ROCK) inhibitor, on postoperative scar formation in human Tenon's fibroblasts. METHODS: Collagen gel contraction assays were used to compare contractility activity among ripasudil and other anti-glaucoma drugs. The effect of Ripasudil in combination with other anti-glaucoma drugs and transforming growth factor-ß (TGF-ß), latanoprost and timolol-induce contractions were also tested in this study. Immunofluorescence and Western blotting were used to study the expression of factors relating scarring formation. RESULTS: Ripasudil inhibited contraction in collagen gel assay and reduced α-smooth muscle actin (SMA) and vimentin (scar formation-related factors) expression, which was inversely promoted by latanoprost, timolol or TGF-ß. Ripasudil also inhibited contraction on TGF-ß, latanoprost and timolol-induced contraction. Furthermore, we investigated the effects of ripasudil on postoperative scarring in a mouse model; ripasudil suppressed postoperative scar formation by altering the expression of α-SMA and vimentin. CONCLUSIONS: These results suggest that ripasudil, ROCK inhibitor may inhibit excessive fibrosis after glaucoma filtering surgery vis inhibition the transdifferentiation of tenon fibroblast into myofibroblast and may have a potential effect as anti-scarring for glaucoma filtration surgery.

Safety and Efficacy of the Rho-Kinase Inhibitor (Ripasudil) in Bleb Needling after Trabeculectomy: A Prospective Multicenter Study.

Ripasudil, a rho-associated protein kinase inhibitor ophthalmic solution, shows a protective effect in preventing excessive scarring in vitro. This study aims to evaluate the safety and efficacy of ripasudil for glaucoma patients submitted to the needling procedure. In this prospective, multicenter, single-arm study, we included 20 eyes of 20 patients with glaucoma who underwent the needling procedure without antimetabolites. All patients administered ripasudil after needling for three months. The primary endpoint of this study was the safety of ripasudil in patients, and the secondary endpoint was the change in IOP at 12 weeks after the needling procedure. No serious complications were found in the patients. One eye experienced pruritus and conjunctival follicle, while another eye had conjunctival follicle. These complications were transient and resolved quickly after discontinuation of ripasudil. The mean preoperative IOP was 14.6 ± 4.6 mmHg, which decreased to 11.0 ± 4.7 mmHg (p = 0.0062) at 1 week postoperatively. The IOP reduction effect continued to 12 weeks (11.8 ± 3.1 mmHg; p = 0.0448). The administration of the ROCK inhibitor, ripasudil, after the needling procedure is safe and effective in maintaining IOP for 12 weeks.

Corneal Endothelial Cell Loss after Ciliary Sulcus Placement of Ahmed Glaucoma Valve in Patients with Noninfectious Uveitic Glaucoma.

This study was performed to investigate the corneal endothelial cell density (CECD) reduction and treatment efficacy in patients with uveitic glaucoma treated by the ciliary sulcus placement of the Ahmed glaucoma valve (AGV). This retrospective study included 27 eyes of 27 patients with noninfectious uveitis who underwent the sulcus placement of the AGV. Each patient underwent a clinical assessment including a CECD measurement before surgery and at 3, 6, 9, and 12 months after surgery. The mean CECD was 2431.4 ± 367.5 cells/mm2 at preoperative baseline and 2360.5 ± 391.3 cells/mm2 at 12 months (p = 0.074), with a reduction rate of 2.73 ± 9.29%. The CECD reduction was significantly greater in patients with unilateral uveitis than that with bilateral uveitis. The rate of successful intraocular pressure control was 88% at 12 months, and the number of intraocular pressure-lowering medications was significantly reduced (p < 0.001). The current study showed that the implantation of an Ahmed tube into the ciliary sulcus provided stable intraocular pressure control in patients with glaucoma secondary to noninfectious uveitis, and CECD reduction was moderate in most patients at 12 months.

Dietary supplement of mushrooms promotes SCFA production and moderately associates with IgA production: A pilot clinical study.

Background: Mushrooms are rich in dietary fiber, and fiber intake has been reported to increase the levels of short-chain fatty acids (SCFAs). It has also been reported that SCFAs promote immunoglobulin A (IgA) production, indicating involvement in systemic immunity. Objectives: The objective of this study was to evaluate the effects of mushroom consumption on the amount of intestinal IgA. We also aimed to comprehensively evaluate the gut microbiota and intestinal metabolome and to conduct an exploratory analysis of their relationship with IgA. Methods: Healthy adults (n = 80) were enrolled in a parallel group trial. Participants consumed a diet with mushrooms or a placebo diet once daily for 4 weeks. Gut microbiota profiles were assessed by sequencing the bacterial 16S ribosomal RNA-encoding gene. Intestinal metabolome profiles were analyzed using capillary electrophoresis-time of flight mass spectrometry (CE-TOFMS). Results: Mushroom consumption tended to increase IgA levels at 4 weeks of consumption compared to those in the control group (p = 0.0807; Hedges' g = 0.480). The mushroom group had significantly higher levels of intestinal SCFAs, such as butyrate and propionate, than the control group (p = 0.001 and 0.020; Hedges' g = 0.824 and 0.474, respectively). Correlation analysis between the changes in the amount of intestinal IgA and the baseline features of the intestinal environment showed that the increasing amount of intestinal IgA was positively correlated with the baseline levels of SCFAs (Spearman's R = 0.559 and 0.419 for butyrate and propionate, respectively). Conclusion: Consumption of mushrooms significantly increased the intestinal SCFAs and IgA in some subjects. The increase in intestinal IgA levels was more prominent in subjects with higher SCFA levels at baseline. This finding provides evidence that mushroom alters the intestinal environment, but the intensity of the effect still depends on the baseline intestinal environment. This trial was registered at www.umin.ac.jp as UMIN000043979.

Treatment outcomes in the neovascular glaucoma tube versus trabeculectomy study.

PURPOSE: To compare surgical outcomes between patients who underwent Baerveldt glaucoma implantation versus trabeculectomy (TLE) for the treatment of neovascular glaucoma. METHODS: We performed a prospective, randomized, controlled clinical trial at Hiroshima University and Tsukazaki Hospital, Japan. Patients were randomized to Baerveldt glaucoma implantation (23 patients) or TLE (27 patients). The primary outcome measure was the rate of intraocular-pressure control. Secondary outcome measures included complications and interventions. We defined "failure" as intraocular pressure ≥ 22 mmHg or < 20% reduction from baseline pressure, on two consecutive follow-up visits; need for additional glaucoma surgery; vision-threatening complications; or loss of light perception. Kaplan-Meier analysis was used to determine surgical success rates. Postoperative complications and interventions were compared between the two groups with Pearson Chi-square tests. RESULTS: There were no significant differences in demographic or ocular characteristics between the treatment groups at baseline. The postoperative follow-up was 26.6 ± 19.4 months in the Baerveldt group and 27.3 ± 20.1 months in the TLE group. There were no statistical differences (Mann-Whitney nonparametric tests with Bonferroni correction) in postoperative intraocular pressure measured at 6-month intervals. Success rates were 59.1 and 61.6% at 1-year after Baerveldt glaucoma implantation and TLE, respectively. Kaplan-Meier analysis showed no significant difference in success between groups (P = 0.71, log-rank test). Medication use, visual acuity, and interventions were similar between groups. Thirteen late postoperative complications developed in the Baerveldt glaucoma implantation group and four complications developed in the TLE group. Tube exposure was the most common late complication. CONCLUSION: These two procedures produced similar surgical success, intraocular-pressure reductions, visual acuity, and number of medications at the last visit. The TLE group showed smaller numbers of late complications and patients who lost more than two lines of visual acuity. Therefore, TLE might be a safer and better way to treat patients with neovascular glaucoma.

Functional analysis of mesencephalic astrocyte-derived neurotrophic factor in retinal ganglion cells under oxidative stress.

Glaucoma is optic neuropathy that is characterized by progressive neurodegeneration of the retinal ganglion cells (RGCs) and axons. This condition will lead to visual impairment and bring glaucoma to become the second cause of blindness globally. Neuroprotection in glaucoma is needed to prevent the progression of optic neuropathy. In this study, we examined the effects of the superior colliculus (SC), and mesencephalic astrocyte-derived neurotrophic factor (MANF) secreted from the SC, on RGC survival after oxidative stress. SC slices and RGCs from rats (3-day old) were co-cultured using a 3D-transwell system. In addition, primary RGCs from 4 to 5-day-old rats were cultured and treated with 100 µM hydrogen peroxide (H2 O2 ), together with stimulation by MANF. Immunoblot and immunofluorescence analyses indicated down-regulated expression levels of several survival markers of RGCs. Extension of neurites was decreased in RGCs treated with 100 µM H2 O2 . Following co-culture with SC slices, or the addition of MANF, we found that both the down-regulated expression of neural markers and extension of neurites caused by oxidative stress in RGCs were blocked. Furthermore, we found a decrease in the expression of neural markers and extension of neurites after co-culture with MANF siRNA-treated SC slices compared with slices treated with mock siRNA, but, RGCs co-cultured with SC slices treated with MANF siRNA displayed no-changed about to apoptosis. These results suggest that MANF secreted from the SC may play an important role in maintenance of function and survival of RGCs. It is also possible that MANF is an important factor in neuroprotection of RGCs. SIGNIFICANCE OF THE STUDY: Glaucoma is a progressive neurodegenerative disease of the retinal ganglion cell (RGC) and their axons. Neuroprotection is aimed at protecting those neurons that are damaged glaucomatous optic neuropathy. We have now examined the effects of superior colliculus, or msencephalic astrocyte-derived neutrophic factor (MANF), secreted from superior colliculus, on RGC survival using co-culture system. Our results suggested that MANF may important key factor in neuroprotection of RGC.