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Mitsuya Otsuka, Naoki Tojo, Hitoshi Yamazaki, Tomoko Ueda-Consolvo, Atsushi Hayashi Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanCorrespondence: Atsushi Hayashi, Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama City, 930-0194, Japan, Tel +81-76-434-7363, Fax +81-76-434-5037, Email ahayashi@med.u-toyama.ac.jpPurpose: We compared the corneal endothelial cell loss between trabeculectomy (Trab) and Ex-Press® surgery (EXP) for low-intraocular pressure (IOP) glaucoma patients.Patients and Methods: This was a single-facility retrospective study. We analyzed the cases of patients with primary open-angle glaucoma (POAG) and pre-operative IOP ≤ 21 mmHg who had undergone Trab or EXP surgery and were followed for > 3 years. Noncontact specular microscopy was used to determine the corneal endothelial cell density (CED) before and after Trab or EXP surgery. We measured the CED at 12, 24, and 36 months post-surgery. We compared the CED values and CED survival ratio after both surgeries using paired t-tests.Results: We included 39 eyes that underwent Trab and 36 eyes that underwent EXP surgery. In the Trab group, the mean CED value had decreased from 2333 ± 399 at baseline to 2066 ± 587 cells/mm2 after 3 years. In the EXP group, the mean CED value had decreased from 2320 ± 393 at baseline to 2229 ± 460 cells/mm2 after 3 years. The survival ratio of CED at > 3 years was 89.3 ± 14.2% (Trab group) and 95.6 ± 11.1% (EXP group); compared to the Trab surgery, the EXP surgery thus significantly decreased the CED loss (p = 0.037). No case resulted in bullous keratopathy.Conclusion: Compared to trabeculectomy, Ex-Press® surgery appears to be a safer surgical method with regard to the endothelial cell loss risk.Keywords: Ex-Press, glaucoma, corneal endothelial cell, trabeculectomy

Mitsuya Otsuka, Naoki Tojo, Shuichiro Yanagisawa, Atsushi Hayashi Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanCorrespondence: Atsushi Hayashi, Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan, Tel +81-76-434-7363, Fax +81-76-434-5037, Email ahayashi@med.u-toyama.ac.jpPurpose: We treated two patients with ciliary detachment due to an ab interno trabeculotomy. The ciliary detachment was improved by the use of sulfur hexafluoride (SF6) gas or octafluoro propane (C3F8) tamponade.Patients and Methods: Patient 1 was a 52-year-old Brazilian man with primary open angle glaucoma (POAG). His preoperative intraocular pressure (IOP) was 29 mmHg. Patient 2 was a 57-year-old Japanese woman with POAG. Her preoperative IOP was 35 mmHg. Both patients underwent an ab interno trabeculotomy with a microhook. They caused ciliary detachment as a postoperative complication. We could observe their ciliary detachment with anterior segment optical coherence tomography (AS-OCT). Hypotony persisted for 2 months and the patients’ ciliary detachment had not improved. They each underwent a pars plana vitrectomy (PPV) with simultaneous 20% SF6 filling.Results: In Patient 1, the use of the SF6 gas tamponade successfully attached the ciliary body. His IOP was increased to 30 mmHg after this resolution of the ciliary detachment. He underwent additional tube shunt surgery. For Patient 2, the SF6 gas tamponade improved the ciliary detachment but the ciliary body could not be attached. We injected 0.6 cc of 100% C3F8 gas into the vitreous cavity, and this gas tamponade was able to attach the ciliary body.Conclusion: AS-OCT is very useful to evaluate ciliary detachment. PPV+Gas tamponade can be a treatment option for ciliary detachment.Keywords: ab interno trabeculotomy, ciliary detachment, cyclodialysis, tamponade, microhook

Naoki Tojo, Atsushi Hayashi Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanCorrespondence: Atsushi HayashiDepartment of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, JapanTel +81-76-434-7363Fax +81-76-434-5037Email ahayashi@med.u-toyama.ac.jpBackground: We compared the efficiency of trabectome surgery for patients with differing preoperative intraocular pressure (IOP) values in a single-facility retrospective study. We evaluated surgical outcomes based on three grades of preoperative IOP: high (hi-IOP, > 26 mmHg), middle (mid-IOP, 18– 26 mmHg), and low (lo-IOP, < 18 mmHg).Patients and Methods: We analyzed the cases of 204 eyes that underwent trabectome surgery and were followed > 2 years. We defined failure as a reduction of IOP < 20% or requiring additional glaucoma surgery. We used 4 cutoff values > 21, > 18, > 15, and > 12 mmHg. Other factors that may affect surgical outcomes were also investigated: age, central corneal thickness (CCT), history of selective laser trabeculotrabculoplasty (SLT), preoperative visual field, and simultaneous cataract surgery.Results: Trabectome surgeries significantly decreased the IOP values from 23.0 ±  7.2 mmHg to 13.6 ±  3.6 mmHg at 2 years post-surgery. The mid-IOP group achieved significantly better surgical outcomes than the lo-IOP and hi-IOP groups with cutoff values 21, 18, and 15 mmHg. A thin CCT and simultaneous cataract surgery were significantly related to better surgical outcomes with cutoff value 21.18 and 15 mmHg.Conclusion: For the patients with preoperative IOP < 18 mmHg, it was difficult to decrease their IOP > 20% with trabectome surgery. Patients with preoperative IOP values > 26 mmHg often required additional glaucoma surgery.Keywords: trabectome, surgical outcome, intraocular pressure, factor, preoperative IOP

Naoki Tojo, Atsushi Hayashi, Mizuki Hamada Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanCorrespondence: Atsushi HayashiDepartment of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama City 930-0194, JapanTel +81-76-434-7363Fax +81-76-434-5037Email ahayashi@med.u-toyama.ac.jpPurpose: Persistent corneal edema is a serious potential complication of Baerveldt glaucoma implant (BGI) surgery. A trabeculectomy reduces the density of corneal endothelial cells. We investigated the effect of BGI surgery on corneal endothelial cells of patients with no history of trabeculectomy.Methods: We retrospectively analyzed 85 eyes of 85 patients who underwent BGI surgery and were followed-up for ≥12 months. We used new criteria for surgical failure. We defined persistent corneal edema or needed additional surgery for changing the tube position due to remarkable reduction in corneal endothelial cells as failure. We compared surgical outcomes with new criteria and the rates of corneal endothelial cell density (ECD) loss after BGI surgery between the anterior chamber insertion (AC) group (n=23) and vitreous cavity insertion (VC) group (n=63).Results: The mean pre-operative ECD values of the AC and VC groups were not significantly different at 2309 ± 498 and 2204 ± 556 (p=0.426). The ECD reduction rate in the AC group was significantly faster than in the VC group. The mean post-operative IOP values significantly decreased in both groups. However, the VC group’s surgical outcomes were significantly better than the AC group’s (p=0.0241) with the new criteria.Conclusion: The mean of ECD did not decrease significantly after BGI surgery in VC group patients with no history of trabeculectomy. BGI surgery insertion to the vitreous cavity was safe and had much less effect on the ECD decrease compared to insertion to the anterior chamber.Keywords: baerveldt, corneal endothelial cells, anterior chamber, vitreous cavity, glaucoma implant surgery

Naoki Tojo, Atsushi Hayashi, Mitsuya Otsuka Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan Purpose: The aim of this study was to investigate the factors influencing the volume of the filtration bleb after Ex-PRESS® surgery.Methods: This was a retrospective non-randomized study. After excluding patients who had undergone an additional glaucoma surgery, 99 glaucoma patients who underwent Ex-PRESS® surgeries and were followed up for >2 years were analyzed. We used anterior segment optical coherence tomography to measure the bleb volume, and compared the volume at 1 year with that at 2 years after surgery. We also examined potential influencing factors, including age, number of medications, central corneal thickness, type of glaucoma, preoperative intraocular pressure (IOP), postoperative IOP, reduction ratio of IOP, history of trabeculotomy, and operation method (Ex-PRESS® surgery only or simultaneous cataract surgery).Results: Ex-PRESS® surgeries significantly decreased the IOP from 26.3±9.7 mmHg to 11.6±3.7 mmHg after 24 months (P

Naoki Tojo, Mitsuya Otsuka, Atsushi Hayashi Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan Purpose: To compare the postoperative interventions and outcomes between conventional trabeculectomy and trabeculectomy with the Ex-PRESS® mini-glaucoma shunt device (Ex-Press).Methods: This was a retrospective, comparative, single-facility study. We analyzed the cases of 108 glaucoma patients who underwent trabeculectomy and were followed for >1 year. Thirty-nine eyes underwent a conventional trabeculectomy (conventional group) and 69 eyes underwent a trabeculectomy with an Ex-Press (Ex-Press group). As evaluation items, we examined postoperative intraocular pressure (IOP), the surgical success rate, postoperative complications, the number of days to laser suture lysis, and needling.Results: Trabeculectomy significantly decreased the patients’ IOP values from 27.8±7.9 to 11.1±3.9 mmHg in the conventional group (p

Naoki Tojo, Shinya Abe, Mari Miyakoshi, Atsushi Hayashi Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan Purpose: Ab interno trabeculectomy (AIT) with the Trabectome has been shown to reduce intraocular pressure (IOP) in eyes with pseudoexfoliation (PEX) glaucoma. Here, we examined the change of IOP fluctuations before and after only AIT or AIT with cataract surgery in PEX patients using the contact lens sensor Triggerfish®.Methods: This was a prospective open-label study. Twenty-four consecutive patients with PEX glaucoma were included. Twelve patients underwent cataract surgery and AIT (triple-surgery group), and 12 patients underwent only AIT (single-surgery group). In each eye, IOP fluctuations over 24 h were measured with the contact lens sensor before and at 3 months after the surgery. We compared the change of IOP fluctuation before and after operation. We also evaluated the difference in IOP changes between the triple- and single-surgery groups.Results: At 3 months after the surgeries, the mean IOP was significantly reduced from 23.5±6.5 mmHg to 14.6±2.8 mmHg in the single-surgery group and from 22.5±3.0 mmHg to 11.5±2.9 mmHg in the triple-surgery group. The mean IOP reduction rate was significantly higher in the triple-surgery group compared to the single-surgery group (p=0.0358). In both groups, the mean range of IOP fluctuations was significantly decreased during nocturnal periods. The mean range of 24 h IOP fluctuations was decreased in the triple-surgery group (p=0.00425), not in the single-surgery group (p=0.970).Conclusion: Triple surgery could decrease IOP value and the IOP fluctuations to a greater extent than single surgery in PEX glaucoma patients. Keywords: pseudoexfoliation, ab interno trabeculectomy, contact lens sensor, fluctuation, intraocular pressure

Naoki Tojo, Shinya Abe, Mari Miyakoshi, Atsushi Hayashi Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan Purpose: We investigated correlations between short-term and long-term intraocular pressure (IOP) fluctuations. Methods: We examined 50 eyes of glaucoma patients who were followed for >2 years. We measured short-term IOP fluctuation using a Triggerfish® contact lens sensor (CLS). The short-term IOP fluctuation (mVeq) was defined as the difference between the maximum value and the minimum value measured during the 24-hour course with CLS. The long-term IOP fluctuation was defined by four parameters: 1) the mean IOP (mmHg) determined during follow-up; 2) the IOP difference, which was defined as the difference between the maximum IOP and the minimum IOP; 3) the standard deviation of IOP; and 4) the peak IOP, which was defined as the maximum IOP. Correlations between these parameters and the short-term IOP fluctuation were examined. Results: The mean follow-up period was 5.4 years. The average IOP was 15.0±4.0 mmHg. The range of short-term IOP fluctuation identified with CLS was significantly correlated with all the four long-term IOP fluctuation parameters. Conclusion: Short-term IOP fluctuations were found to be associated with long-term IOP fluctuations. Examination of 24-hour IOP fluctuations with the CLS might be useful for predicting the long-term IOP fluctuation. Keywords: intraocular pressure, contact lens sensor, Triggerfish®, fluctuation

Naoki Tojo, Atsushi Hayashi, Akio Miyakoshi Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan Purpose: To report a case of corneal decompensation due to the Ex-PRESS® mini glaucoma shunt device (Ex-PRESS).Patient and methods: A 75-year-old man had pseudoexfoliation glaucoma in his right eye. He underwent filtration surgery with Ex-PRESS. His intraocular pressure was 7 mmHg after 9 months.Results: We observed partial decompensation of the corneal endothelium adjacent to the filtering bleb. Specular microscopy revealed a marked decrease in the endothelial cell density at the center of the cornea.Conclusion: Anterior segment optical coherence tomography is very useful for evaluating corneal edema and the position of Ex-PRESS. It is important to follow up with an examination of the corneal endothelial cells. Keywords: Ex-PRESS, bullous keratopathy, trabeculectomy, complication, cornea

Naoki Tojo Tomoko Nakamura Hironori Ozaki Miyako Oka Toshihiko Oiwake Atsushi HayashiDepartment of Ophthalmology, University of Toyama, Toyama, JapanPurpose: To investigate changes in cone photoreceptors with adaptive optics (AO) fundus imaging and spectral domain optical coherence tomography (SD-OCT) in a case of occult macular dystrophy (OMD).Patient and methods: Both eyes of a 42-year-old woman diagnosed with OMD were examined. We used an AO fundus camera to obtain images of cone photoreceptors in the macula of the OMD subject and five healthy control subjects. Correlations between the AO images and the SD-OCT images were examined. Cone photoreceptors in eight areas in the macula of OMD and healthy control subjects were analyzed and compared.Results: SD-OCT showed a loss of the cone outer-segment tips line outside of the fovea in both eyes of the subject with OMD. The left eye with decreased visual acuity showed a discontinuous photoreceptor inner-segment and outer-segment line and cone outer-segment tips line at the fovea in SD-OCT and loss of cone mosaics as a dark spot in the AO image. In panoramic AO images and cone-density maps, less cone density was observed in a ring-like region outside the fovea than in the peripheral retina. In most of the areas examined, the cone densities were lower in the OMD eyes than in the healthy control eyes.Conclusions: Cone densities in the macula of the OMD patient were greatly decreased. AO images were found to be useful to evaluate morphologic changes in cone photoreceptors in patients with OMD.Keywords: occult macular dystrophy, adaptive optics, cone photoreceptor, cone analysis, optical coherence tomography

Naoki Tojo, Tomoko Nakamura, Chiharu Fuchizawa, Toshihiko Oiwake, Atsushi HayashiDepartment of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanBackground: The purpose of this study was to examine cone photoreceptors in the macula of patients with retinitis pigmentosa using an adaptive optics fundus camera and to investigate any correlations between cone photoreceptor density and findings on optical coherence tomography and fundus autofluorescence.Methods: We examined two patients with typical retinitis pigmentosa who underwent ophthalmological examination, including measurement of visual acuity, and gathering of electroretinographic, optical coherence tomographic, fundus autofluorescent, and adaptive optics fundus images. The cone photoreceptors in the adaptive optics images of the two patients with retinitis pigmentosa and five healthy subjects were analyzed.Results: An abnormal parafoveal ring of high-density fundus autofluorescence was observed in the macula in both patients. The border of the ring corresponded to the border of the external limiting membrane and the inner segment and outer segment line in the optical coherence tomographic images. Cone photoreceptors at the abnormal parafoveal ring were blurred and decreased in the adaptive optics images. The blurred area corresponded to the abnormal parafoveal ring in the fundus autofluorescence images. Cone densities were low at the blurred areas and at the nasal and temporal retina along a line from the fovea compared with those of healthy controls. The results for cone spacing and Voronoi domains in the macula corresponded with those for the cone densities.Conclusion: Cone densities were heavily decreased in the macula, especially at the parafoveal ring on high-density fundus autofluorescence in both patients with retinitis pigmentosa. Adaptive optics images enabled us to observe in vivo changes in the cone photoreceptors of patients with retinitis pigmentosa, which corresponded to changes in the optical coherence tomographic and fundus autofluorescence images.Keywords: adaptive optics fundus camera, cone photoreceptor, fundus autofluorescence, optical coherence tomography, retinitis pigmentosa

Summary: Characterizing perturbation of molecular pathways in congenital Zika virus (ZIKV) infection is critical for improved therapeutic approaches. Leveraging integrative systems biology, proteomics, and RNA-seq, we analyzed embryonic brain tissues from an immunocompetent, wild-type congenital ZIKV infection mouse model. ZIKV induced a robust immune response accompanied by the downregulation of critical neurodevelopmental gene programs. We identified a negative correlation between ZIKV polyprotein abundance and host cell cycle-inducing proteins. We further captured the downregulation of genes/proteins, many of which are known to be causative for human microcephaly, including Eomesodermin/T-box Brain Protein 2 (EOMES/TBR2) and Neuronal Differentiation 2 (NEUROD2). Disturbances of distinct molecular pathways in neural progenitors and post-mitotic neurons may contribute to complex brain phenotype of congenital ZIKV infection. Overall, this report on protein- and transcript-level dynamics enhances understanding of the ZIKV immunopathological landscape through characterization of fetal immune response in the developing brain.

Abstract. It was found that human serum stored for 2 months at 4°C (modified serum) induced monocyte proliferation and simultaneous macrophage colony stimulating factor (M-CSF) production by these cells in vitro . Cell number, estimated by DNA content, doubled after 10 days in culture in the presence of modified serum, while it decreased in culture with freshly thawed control serum. As the addition of more than 2.5 ng/ml of recombinant M-CSF significantly supported monocyte survival/proliferation, cells were cultured for 10 days in medium supplemented with control serum, and endogenous M-CSF production was investigated by enzyme-linked immunosorbent assay. M-CSF concentration in the supernatants was 15–30 ng/ml after 10 day in culture with modified serum, a level that might be sufficient for monocyte proliferation. The modified serum induced M-CSF from freshly isolated monocytes, while M-CSF was hardly detected in cultures supplemented with control serum. Assay for peroxidized lipid and agarose gel electrophoresis demonstrated that the modified serum contained more oxidized low density lipoproteins (LDL) than the control serum. Ligands of scavenger receptors, which are receptors for oxidized LDL, such as dextran sulphate, polyinosinic acid, heparin and acetylated LDL also significantly induced M-CSF production from human monocytes, although this was at levels below 2 ng/ml. These results indicate that serum modified by oxidation stimulates monocytes to produce M-CSF resulting in their proliferation, and that signalling via scavenger receptors is one of the mechanisms responsible for this induction of M-CSF. [ABSTRACT FROM AUTHOR]

Purpose: We compared the corneal endothelial cell loss between trabeculectomy (Trab) and Ex-Press ® surgery (EXP) for low-intraocular pressure (IOP) glaucoma patients., Patients and Methods: This was a single-facility retrospective study. We analyzed the cases of patients with primary open-angle glaucoma (POAG) and pre-operative IOP ≤ 21 mmHg who had undergone Trab or EXP surgery and were followed for >3 years. Noncontact specular microscopy was used to determine the corneal endothelial cell density (CED) before and after Trab or EXP surgery. We measured the CED at 12, 24, and 36 months post-surgery. We compared the CED values and CED survival ratio after both surgeries using paired t-tests., Results: We included 39 eyes that underwent Trab and 36 eyes that underwent EXP surgery. In the Trab group, the mean CED value had decreased from 2333 ± 399 at baseline to 2066 ± 587 cells/mm2 after 3 years. In the EXP group, the mean CED value had decreased from 2320 ± 393 at baseline to 2229 ± 460 cells/mm 2 after 3 years. The survival ratio of CED at >3 years was 89.3 ± 14.2% (Trab group) and 95.6 ± 11.1% (EXP group); compared to the Trab surgery, the EXP surgery thus significantly decreased the CED loss (p = 0.037). No case resulted in bullous keratopathy., Conclusion: Compared to trabeculectomy, Ex-Press ® surgery appears to be a safer surgical method with regard to the endothelial cell loss risk., Competing Interests: No potential conflict of interest was reported by the authors., (© 2024 Otsuka et al.)

Purpose: We compared corneal endothelial cell (CED) loss after Ex-Press (EXP) surgery between patients with primary open-angle glaucoma (POAG) and pseudo-exfoliation glaucoma (PEX)., Patients and Methods: This was a single-facility retrospective study. We included glaucoma patients who had undergone EXP surgery and were followed up > 3 years. We measured the CED before and after (at 12, 24, and 36 months) EXP surgery by noncontact specular microscopy and compared the means of the CED values and CED survival ratios after EXP surgery by paired t-test., Results: We included 119 eyes that underwent EXP surgery, including 60 POAG eyes and 59 PEX eyes. In the POAG group, the mean CED decreased from 2389 ± 321 at baseline to 2230 ± 424 cells/mm 2 after 3 years. In the PEX group, the mean CED decreased from 2111 ± 510 at baseline to 1845 ± 628 cells/mm 2 after 3 years. At the 3-year follow-up, the CED survival ratio was 93.3 ± 12.5% in the POAG group and significantly lower, at 85.0 ± 19.5%, in the PEX group (p = 0.0064). Two cases in the PEX group developed bullous keratopathy., Conclusions: EXP surgery decreased the corneal endothelial cell populations in PEX patients faster than POAG patients., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Previously, we reported that the Ex-press® shunt (EXP) was associated with more rapid reduction in corneal endothelial cells when inserted into the cornea rather than the trabecular meshwork (TM). We compared the reduction rate of corneal endothelial cells between the corneal insertion group and TM insertion group., Methods: This was a retrospective study. We included patients who had undergone EXP surgery and were followed for > 5 years. We analyzed the corneal endothelial cell density (ECD) before and after EXP implantation., Results: We included 25 patients in the corneal insertion group and 53 patients in the TM insertion group. One patient in the corneal insertion group developed bullous keratopathy. The ECD decreased significantly more rapidly in the corneal insertion group (p < 0.0001), in whom the mean ECD decreased from 2227 ± 443 to 1415 ± 573 cells/mm 2 at 5 years with a mean 5-year survival rate of 64.9 ± 21.9%. By contrast, in the TM insertion group, the mean ECD decreased from 2356 ± 364 to 2124 ± 579 cells/mm 2 at 5 years, and the mean 5-year survival rate was 89.3 ± 18.0%. The decrease rate of ECD was calculated as 8.3%/year in the corneal insertion group and 2.2%/year in the TM insertion group., Conclusions: Insertion into cornea is a risk factor for rapid ECD loss. The EXP should be inserted into the TM to preserve the corneal endothelial cells., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: It has been reported that corneal endothelial cells (CEC) decrease faster when the tip of the Baerveldt glaucoma implant (BGI) tube is inserted into the anterior chamber than into the vitreous cavity. We investigated whether surgically relocating the tip of the BGI tube from the anterior chamber to the vitreous cavity could reduce CEC loss., Patients and Methods: This was a single facility retrospective cohort study. The inclusion criteria were the CEC density less than 1500 cells/mm 2 and the CEC reduction ratio was greater than 10%/year. The subjects were 11 consecutive patients that could be followed > 12 months after relocation surgery. All patients were undergone vitrectomy, and the tip of tube was inserted into the vitreous cavity from the anterior chamber. We compared the intraocular pressure (IOP), reduction slope of CEC density and annual reduction rate of CEC density before and after relocation surgery. We calculated the annual reduction ratio in comparison with the preoperative CEC density (%/year)., Results: The mean of period between the Baeveldt with anterior chamber insertion surgery and the relocation surgery was 33.8 ± 15.0 months. The mean of follow-up after relocation surgery was 21.8 ± 9.8 months. The relocation surgery did not significantly change IOP (p = 0.974). The mean preoperative and postoperative IOP were 13.1 ± 4.5 and 13.6 ± 4.3 mmHg. The reduction ratio of the CEC density was 15.4 ± 6.7 (%/year) before relocation surgery and significantly slower at 8.3 ± 6.5 (%/year) after relocation surgery (p = 0.024). Two patients resulted in bullous keratopathy after relocation surgery., Conclusions: Relocating the tip of BGI tube from the anterior chamber to the vitreous cavity could reduce CEC loss., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To compare surgical outcomes of Ex-PRESS® (EXP) surgery for primary open-angle glaucoma (POAG) between low preoperative intraocular pressure (IOP) and high preoperative IOP., Methods: This was a retrospective non-randomized study. Seventy-nine POAG patients who underwent EXP surgery and were followed for > 3 years were included. Patients with a preoperative IOP of ≦ 16 mmHg and > 16 mmHg with tolerant glaucoma medications were defined as the low IOP group and the high IOP group, respectively. We compared the surgical outcomes, postoperative IOP and number of glaucoma medications. Success was defined as a postoperative IOP of ≦ 15 mmHg and a reduction of > 20% from the preoperative IOP to the postoperative IOP., Results: EXP surgeries significantly decreased IOPs from 13.2 ± 2.0 to 9.1 ± 2.9 mmHg in the low IOP group (p < 0.001), and from 22.5 ± 4.8 to 12.5 ± 4.0 mmHg in the high IOP group (p < 0.001). The mean postoperative IOP was significantly low in the low IOP group at 3 years (p = 0.0008). Success rates compared using the Kaplan-Meier survival curve were not significantly different (p = 0.449)., Conclusions: EXP surgery was useful for POAG patients with a low preoperative IOP., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

This study conducted fundamental research to develop a more effective BNCT targeting cancer stem cells. We constructed plasmids that induced the overexpression of L-type amino acid transporter 1 (LAT1) tagged with tdTomato on the cytoplasmic membranes of CD133 expressing cancer cells. After transfection of the plasmids into a glioblastoma cell line (T98G), several clones overexpressing LAT1-tdTomato in the hypoxic microenvironment of the spheroids formed from each clone were obtained. Confocal laser microscopic observation confirmed that signals from LAT1-tdTomato overlapped with immunofluorescence signals from the second antibody binding to CD133 in the hypoxic microenvironment of the spheroids. As CD133-positive cells in the hypoxic microenvironment of T98G spheroids have cancer stem cell characteristics, LAT1 seems to be selectively overexpressed in cancer stem cell-like cells. An RI tracer method showed that cells overexpressing LAT1-tdTomato in the hypoxic microenvironment of spheroids incorporate 14C-BPA much more than cells that do not overexpress LAT1-tdTomato. Neutron radiation experiments showed a more significant regression in spheroids formed with clones than in spheroids formed with parental cells when spheroids were treated with 10BPA. These results suggest that BNCT combined with gene therapy targeting cancer stem cells is more effective in glioblastoma therapy., (©2023 by Radiation Research Society. All rights of reproduction in any form reserved.)

Purpose: To investigate the risk factors for Ex-Press ® (EXP) surgery failure., Patients and Methods: This was a retrospective non-randomized study of 98 patients who had undergone EXP and were followed up ≥ 5 years. We investigated the following nine risk factors: age, gender, hypertension, diabetes mellitus (DM), previous glaucoma surgery, type of glaucoma (primary open-angle glaucoma vs. pseudo-exfoliation glaucoma), surgical methods (EXP alone vs. EXP + cataract surgery simultaneously), central corneal thickness (CCT), and preoperative intraocular pressure (IOP). We defined a successful surgery as a postoperative reduction in the IOP ≥ 20% from the preoperative IOP and ≤ 18 mmHg. We determined the risk factors using multivariate cox regression models., Results: Performing EXP significantly decreased the IOP (preoperative: 25.2 ± 8.7, at 5 years: 11.1 ± 4.1). The success ratio of EXP was 67.4% at 5 years. We found no significant risk factors for EXP surgery failure. The p values of the factors were age (p = 0.936), gender (p = 0.0587), hypertension (p = 0.409), DM (p = 0.967), previous glaucoma surgery (p = 0.940), type of glaucoma (p = 0.435) surgical methods (p = 0.521), CCT (p = 0.091), and preoperative IOP (p = 0.082)., Conclusions: No preoperative factors that could be used to predict the failure of EXP surgery were identified. EXP can be safely performed for primary open-angle glaucoma and pseudo-exfoliation glaucoma., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To compare surgical outcomes between Ex-PRESS® surgery (EXP) and trabeculectomy (Trab) for primary open-angle glaucoma (POAG) with low preoperative intraocular pressure (IOP)., Patients and Methods: This was a retrospective non-randomized study. We included POAG patients with preoperative IOP ≤ 16 mmHg who were taking tolerance glaucoma medications. We compared the surgical outcomes, postoperative IOP, number of glaucoma medications, reduction rate of corneal endothelial cell density (ECD), visual acuity, and postoperative complications between POAG patients who underwent EXP (34 eyes) or Trab (38 eyes) and could be followed up for > 2 years., Results: Both surgeries significantly decreased the IOP (p < 0.001): At 2 years, EXP provided decreases from 13.4 ± 2.3 to 10.2 ± 3.1 mmHg, and Trab provided decreases from 13.5 ± 2.0 to 8.9 ± 3.2 mmHg. No significant differences were observed in the postoperative IOP (p = 0.076), number of postoperative medications (p = 0.263), success rate (p = 0.900), reduction rate of ECD (p = 0.410), or difference in visual acuity (p = 0.174). The reduction rate of IOP was significantly high in the Trab group (p = 0.047)., Conclusions: Both surgeries significantly decreased IOP and were useful surgical methods for low-IOP glaucoma. Our results suggest that trabeculectomy can decrease IOP more than Ex-PRESS surgery but might have more complications., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Prcis: Twenty-four-hour IOP measurements with a CLS showed that among IOP indicators studied, the range of IOP fluctuation was most important and significantly larger in NTG eyes compared with nonglaucoma eyes., Purpose: We conducted the present study to determine (1) the best factor for distinguishing normal tension glaucoma (NTG) and nonglaucoma subjects based on the intraocular pressure (IOP) values measured by a CLS and (2) the optimal cutoff values of that factor., Subjects and Methods: The eyes of 18 nonglaucoma subjects and 26 NTG patients were examined. We evaluated 5 indicators: maximum IOP value, SD, IOP fluctuation range, the cosine-fit curve amplitude, and the amplitude of dual-harmonic regression values. We determined the indicators' cutoff values to distinguish between nonglaucoma subjects and NTG patients with the area under the curve., Results: The mean IOP values were 12.3±2.7 mm Hg in the nonglaucoma eyes and 12.5±3.1 mm Hg in the NTG eyes ( P =0.824). All 5 indicators were significantly higher in the NTG group. The best factor to distinguish the nonglaucoma subjects and NTG patients was the IOP fluctuation range ( P <0.0001, area under the curve=0.844); the cutoff level value was 436.5 millivolt equivalents., Conclusions: Twenty-four-hour IOP measurements with a CLS showed that among IOP indicators studied, the range of IOP fluctuation was most important and significantly larger in NTG eyes compared with nonglaucoma eyes., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The present study examined the radiosensitization induced by a heat shock protein 90 inhibitor, N-vinylpyrrolidone (NVP)-AUY922, in CD133-positive cells in a hypoxic area of T98G spheroids. CD133-positive cells that are induced in the hypoxic microenvironment of spheroids have previously been reported to exhibit cancer stem cell-like properties. The present study used CD133-positive cells from a glioblastoma cell line (T98G) as cancer stem cell-like cells. CD133-positive and negative cells were sorted from T98G spheroids using fluorescence-activated cell sorting and used for colony formation assay. Colony formation assay results indicated that NVP-AUY922 enhanced radiosensitivity more strongly in CD133-positive cells compared with CD133-negative cells. This result showed that NVP-AUY922 was a preferential radiosensitization candidate targeting glioblastoma cancer stem cells. The mechanisms underlying radiosensitization by NVP-AUY922 are discussed in relation to the properties of cancer stem cells. Overall, HIF-1α inhibition by NVP-AUY922 may induce higher sensitization of cancer stem cells to radiation., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Tani et al.)

Background: We report the results of Baerveldt glaucoma implant (BGI) surgery performed with the scleral flap and patch technique., Patients and Methods: This was a retrospective analysis of 97 consecutive patients (107 eyes) who underwent BGI surgery with the scleral flap and patch, and were followed up for >1 year. We evaluated the patients' post-operative intraocular pressure (IOP), corneal endothelial cell density, and complications (corneal edema, Hoffmann elbow exposure)., Results: The preoperative IOP was 32.9 ± 8.6 mmHg. BGI surgery significantly decreased the IOP to 11.1 ± 3.8, 11.3 ± 3.6, 11.3 ± 4.2, 10.7 ± 3.8, and 11.4 ± 3.2 mmHg at 1, 2, 3, 4, and 5 years post-surgery ( p  < 0.001), respectively. The success rates at 1, 2, 3, 4, and 5 years were 96.3%, 94.8%, 94.8%, 88.5%, and 88.5%, respectively. Failure occurred in six eyes. The reasons for failure were as follows: a postoperative IOP ⩾21 mmHg in one patient, and loss of light sensation in five patients. No patients required additional glaucoma surgery. There were no cases of Hoffmann elbow erosion. Corneal edema occurred in five patients., Conclusion: BGI surgery performed with the scleral flap and patch significantly decreased the IOP, and no case of Hoffmann elbow erosion was observed over the 5-year post-operative period.

In this study, we examined the phenotypes of CD133-positive cells that were induced in a hypoxic microenvironment of spheroids formed using a glioblastoma cell line (T98G). Colony-formation assay showed that spheroid CD133-positive cells (SCPCs) were more resistant to X-rays and Temozolomide (TMZ) than spheroid CD133-negative cells (SCNCs) sorted from T98G spheroids. In contrast, the sensitivity to X-rays and TMZ was not different between hypoxic cells and normoxic cells of T98G spheroids in a colony-formation assay using green fluorescent protein (GFP) reporter-transfectants to monitor hypoxia. This result suggests that the difference in the sensitivity to X-rays and TMZ between SCPCs and SCNCs did not result from hypoxia. Transwell membrane assay indicated that the migration and inversion ability of SCPCs was higher than that of SCNCs. These results, including the findings obtained previously regarding nestin positivity in SCPCs, strongly suggest that SCPCs are cancer stem cell (CSC)-like cells. Additionally, based on experiments of monolayer culture of T98G cells, it was shown that hypoxia or low pH culture condition is not sufficient for the induction of SCPCs. The three-dimensional cell structure might be a critical factor for SCPC induction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To compare surgical outcomes between Ex-Press ® (EXP) and Baerveldt glaucoma implant (BGI) surgeries for primary open-angle glaucoma (POAG) and pseudo-exfoliation glaucoma (PEXG) patients., Patients and Methods: This was a retrospective single-facility study. The inclusion criteria were that the patient's preoperative intraocular pressure (IOP) was > 21 mmHg and the post-surgery follow-up was > 1 year. We recruited 161 patients who had undergone a trabeculectomy with EXP (89 eyes) or BGI surgery (72 eyes). We compared these groups' postoperative IOP values and postoperative glaucoma medications, the reduction rate of corneal endothelial cell density (ECD), surgical outcomes, complications, the hospital stay duration, and the number of visits within 3 months post-surgery., Results: Both the EXP and BGI surgeries could significantly decrease the IOP. When the surgical success was defined postoperative IOP ≤ 21 mmHg, the surgical outcome of BGI was significantly better than EXP (p = 0.0148). When the surgical success was defined postoperative IOP ≤ 18, 15 , and 12 mmHg, the surgical outcomes between BGI and EXP surgeries were not significantly different (p = 0.0815, p = 0.331, and p = 0.910). The mean ECD reduction rate was significantly faster in the EXP group. The BGI patients had significantly shorter stays in the hospital and fewer visits within 3 months post-surgery (p < 0.0001)., Conclusions: BGI surgery could provide comparable surgical outcomes as EXP surgery for POAG or PEXG patients with high preoperative IOP. BGI surgery has some advantages: fewer post-surgery visits, less postoperative interventions, and a lower ECD reduction rate.

Background: Several methods can be applied for a trabeculotomy, including the uses of thread, a blade, cauterization, and a hook. We compared the outcomes of trabectome surgery and microhook surgery., Methods: We analyzed the cases of 133 eyes that underwent trabectome (72 eyes) or microhook (61 eyes) surgery and were followed for > 1 year. We defined failure as a < 20% reduction in the postoperative intraocular pressure (IOP) value or requiring additional glaucoma surgery. We used three surgical success definitions: ≤ 21, ≤ 18, and ≤ 15 mmHg IOP reduction. A Kaplan-Meier survival analysis was performed for the surgical outcomes. We compared the trabectome and microhook groups' postoperative IOP values, number of glaucoma medications, and postoperative complications., Results: At 1 year postsurgery, the trabectome surgeries decreased the IOP significantly from 24.6 ± 7.3 to 13.3 ± 3.7 mmHg, and the microhook surgeries significantly decreased the IOP from 24.1 ± 9.2 to 12.5 ± 3.9 mmHg. The two groups' 1-year postoperative IOP values were not significantly different (p = 0.310). The surgical outcomes of the trabectome surgeries were significantly better than those of the microhook surgeries (≤ 21 mmHg: p = 0.0049, ≤ 18 mmHg: p = 0.0029, and ≤ 15 mmHg: p = 0.0393). There were three patients with ciliary detachment in the microhook surgery group., Conclusions: Trabectome surgery provided significantly better surgical outcomes than microhook surgery. The risk of postoperative ciliary detachment should be considered in microhook surgery cases.

Purpose: We investigated glaucoma patients' complications, subjective symptoms, and side effects of continuous 24-h measurement of intraocular pressure (IOP)-related patterns with a contact lens sensor (CLS). We asked the patients to complete a questionnaire about their subjective symptoms after wearing the CLS., Materials and Methods: This was an observational single-facility study. We analyzed 56 patients (35 men, 21 women) who underwent 24-h continuous measurement of their IOP-related patterns with a Triggerfish ® CLS. The four questionnaire items asked whether blurred vision, ocular pain, conjunctival hyperemia, and sleep disorder were present/absent. All questionnaire items were answered subjectively. We examined the relationship between the patients' questionnaire results and their visual acuity and visual field., Results: The rate of blurred vision was 55%; ocular pain, 30%; conjunctival hyperemia, 14%; sleeping disorder, 29%. Patients with good visual acuity tended to report experiencing blurred vision., Conclusions: When 24-h continuous measurement of IOP-related patterns with a CLS is considered, clinicians should tell the patient about the possibility of blurred vision, ocular pain, conjunctival hyperemia, and/or sleeping disorder.

The purpose of this retrospective study was to evaluate the effectiveness of blepharoptosis surgery in patients with deepening of the upper eyelid sulcus (DUES). This case series included 10 consecutive patients (19 eyes) with DUES associated with use of a prostaglandin analog for glaucoma. Patients who had used bimatoprost and developed DUES were changed to an alternative prostaglandin analog and observed for ≥3 months. If there was no improvement, they underwent levator resection for blepharoptosis and were followed up for ≥6 months postoperatively. Improvement in margin reflex distance-1 and surgical complications was evaluated. After discontinuation of bimatoprost in 3 cases (6 eyes), mild subjective and objective improvement in DUES was seen in 2 cases (4 eyes) but without improvement in blepharoptosis. The prostaglandin analog used before surgery was travoprost in 4 eyes (21.0%), tafluprost in 7 eyes (36.9%; including 4 eyes switched from bimatoprost), and latanoprost in 8 eyes (42.1%; including 2 eyes switched from bimatoprost). The mean margin reflex distance-1 value was 1.11 ± 0.96 mm before surgery and 3.72 ± 0.81 mm at the final postoperative follow-up; the difference was significant (P = 3.32 × -10). There were no intraoperative or postoperative complications. Levator resection is a useful and safe procedure for blepharoptosis with DUES.

Purpose: We investigated the factors that influence the reduction in corneal endothelial cells after Ex-Press ® surgery., Methods: This was a retrospective study. We included patients who had undergone Ex-Press surgery and were followed up for > 2. We analyzed the corneal endothelial cell density (ECD) before and after Ex-Press surgery. We investigated the insertion position (Ex-Press device was inserted into cornea or trabecular meshwork (TM)), Ex-Press-iris touch, cornea-iris touch, peripheral anterior synechiae, history of trabeculotomy, history of selective laser trabeculoplasty, type of glaucoma, and simultaneous cataract surgery as influencing factors. We used multivariate analysis to determine the factors influencing the reduction rate of ECD., Results: We included 129 eyes. The mean of ECD had decreased 7.0% at 2 years. Ex-Press surgeries significantly decreased the ECD after 2 years (p = 0.0118). As a result of the multivariate analysis, the factor that led to a significantly faster reduction in ECD was the insertion position of the Ex-Press (p < 0.0001). The reduction rate of ECD after 2 years in cases of insertion into the cornea (27 eyes) was 15.1 ± 3.6%, and in cases of insertion into a TM (102 eyes), it was 5.2 ± 1.4%., Conclusions: Insertion into the cornea was a risk factor for rapid ECD loss. The Ex-Press should be inserted into a TM for long-term protection of the corneal endothelial cells.

Purpose: We examined whether a contact lens sensor (CLS) is useful for the postoperative evaluation of trabectome surgery. We investigated the correlations between the outcomes of trabectome surgery and the output of a CLS., Methods: We examined 24 consecutive eyes of patients with pseudo-exfoliation glaucoma. In each eye, the intraocular pressure (IOP) fluctuations over 24 h were measured with the SENSIMED Triggerfish CLS before and at 3 months after the trabectome surgery. We divided the patients into success (n = 12 eyes) and failure (n = 12 eyes) groups; success was defined as a postoperative IOP level ≤ 21 mmHg plus an IOP reduction ≥ 20% relative to the preoperative IOP value with or without anti-glaucoma medications. We investigated CLS parameters that correlate with surgical outcomes by performing a Cox hazard regression analysis. We determined the maximum value, minimum value, and range of IOP fluctuation as CLS parameters., Results: The mean follow-up period was 38.0 ± 3.0 months. The success rate was 50%. The postoperative range of IOP fluctuation during the nocturnal period with the CLS was significantly correlated with the surgical results (p = 0.024)., Conclusions: A smaller range of IOP fluctuation was significantly correlated with better surgical outcomes. We were able to predict the surgical success after trabectome surgery at 3 months using the CLS. Thus, CLS results could be a new surgical evaluation parameter.