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Purpose To elucidate the non-inferiority of ab interno microhook trabeculotomy (μTLO) using a recently developed reusable stainless spatula-type microhook device to incise the trabecular meshwork to trabectome (TOM) in terms of the 1-year postoperative outcomes of Japanese patients with glaucoma by means of propensity score analyses. Design A multicenter retrospective cohort study. Participants We enrolled 553 and 392 patients who underwent TOM and μTLO, respectively, between January 2014 and March 2020 at 10 facilities. Methods Logistic regression analysis was conducted to calculate the propensity score, which indicates the likelihood of treatment assignment (TOM or μTLO). We set the following factors as outcome-related covariates: age, sex, facility, glaucoma disease types, preoperative intraocular pressure (IOP), glaucoma drug score, mean deviation of the Humphrey visual field test and antithrombotic drug use, the presence or absence of combined cataract surgery, and incision range of trabecular meshwork (one or two quadrants). We analyzed four different methods (matching, inverse probability of treatment weighting (IPTW), stratification, and regression adjustment) using the propensity score. We set 15% as the non-inferiority margin based on previous trabectome meta-analysis results. Main outcome measures The primary outcome was surgical success at 1 year postoperatively. We defined surgical success as satisfying all three criteria: (1) IOP within 5–21 mmHg; (2) IOP reduction of ≥20% from preoperative IOP; and (3) no additional glaucoma surgery. Results The 95% confidence interval of risk difference of surgical failure in μTLO in reference to TOM was −12.1 to +9.5% in matching, −12.7 to +11.1% in IPTW, −12.2 to +7.0 in stratification, and −9.7 to +8.1% in regression adjustment, all of which fell within the predetermined non-inferiority margin of 15%. Conclusions Surgical success of μTLO at 1-year postoperatively was not inferior to that of TOM.

We investigated the shear modulus-passive force relationship in the hip adductor longus (AL) muscles of human cadavers and explored the effect of muscle architecture on the elastic properties of the AL muscle using shear wave elastography (SWE). Nine AL muscles were harvested from a soft, embalmed cadaver. The AL muscles were affixed to a custom-built device comprising two clamps, a pulley, and a cable to provide passive loads, which were increased from 0 to 600 g in 60-g increments. The shear modulus of the AL muscle was measured in the proximal (Pro), middle (Mid), and distal (Dis) regions. The masses and anatomical cross-sectional areas (ACSAs) of the AL muscles were measured. The shear modulus-passive load relationship of each tested muscle region was analyzed by fitting a least-squares regression line. Moreover, the rate of increase in the shear modulus per unit load (s) was calculated. The shear modulus and passive force were linearly correlated for all AL muscles in each region (p 0.01). The mean coefficients of determination (R

Paget's disease of bone (PDB) is a skeletal disorder characterized by disorganized bone remodeling due to abnormal osteoclasts. Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) gene encodes the receptor activator of nuclear factor kappa B (RANK), which has a critical role in osteoclast function. There are five types of rare PDB and related osteolytic disorders due to TNFRSF11A tandem duplication variants so far, including familial expansile osteolysis (84dup18), expansile skeletal hyperphosphatasia (84dup15), early-onset familial PDB (77dup27), juvenile PDB (87dup15), and panostotic expansile bone disease (90dup12).We reviewed a Japanese family with PDB, and performed whole-genome sequencing to identify a causative variant.This family had bone symptoms, hyperphosphatasia, hearing loss, tooth loss, and ocular manifestations such as angioid streaks or early-onset glaucoma. We identified a novel duplication variant of TNFRSF11A (72dup27). Angioid streaks were recognized in Juvenile Paget's disease due to loss-of-function variants in the gene TNFRSF11B, and thought to be specific for this disease. However, the novel recognition of angioid streaks in our family raised the possibility of occurrence even in bone disorders due to TNFRSF11A duplication variants and the association of RANKL-RANK signal pathway as the pathogenesis. Glaucoma has conversely not been reported in any case of Paget's disease. It is not certain whether glaucoma is coincidental or specific for PDB with 72dup27.Our new findings might suggest a broad spectrum of phenotypes in bone disorders with TNFRSF11A duplication variants.

Zr-based metallic glasses are prepared by quenching supercooled liquid under pressure. These glasses are stable in ambient conditions after decompression. The High Pressure Quenched glasses have a distinct structure and properties. The pair distribution function shows redistribution of the Zr-Zr interatomic distances and their shift towards smaller values. These glasses exhibit higher density, hardness, elastic modulus, and yield stress. Upon heating at ambient pressure, they show volume expansion and distinct relaxation behavior, reaching an equilibrated state above the glass transition. These experimental results are consistent with an idea of pressure-induced low to high density liquid transition in the supercooled melt.

To compare the surgical outcomes between Baerveldt glaucoma implant (BGI) surgery and trabeculectomy with mitomycin C for patients with neovascular glaucoma (NVG).Retrospective clinical cohort study at 5 clinical centers in Japan.Patients treated with trabeculectomy or BGI for NVG between April 1, 2012, and December 31, 2019, at 5 clinical centers were recruited.The inclusion criteria were age ≥ 20 years and having NVG. The exclusion criteria were eyes with no light perception vision and with previous tube-shunt surgery. If both eyes in the same patient satisfied the inclusion criteria, the eye that was treated first was investigated. We included 100 eyes undergoing BGI surgery and 204 eyes undergoing trabeculectomy.The primary outcome was surgical success or failure, with failure being defined according to 3 criteria:20% reduction of the preoperative intraocular pressure (IOP) or criterion A (IOP21 mmHg), criterion B (IOP17 mmHg), or criterion C (IOP14 mmHg). Cases of reoperation, a loss of light perception vision, or hypotony were also considered failures.The probability of success was significantly higher in patients undergoing BGI surgery than in those receiving trabeculectomy for criteria A (P0.01) and B (P = 0.01). Trabeculectomy was significantly associated with surgical failure in the multivariable analysis for criterion A (hazard ratio, 1.70) and criterion B (hazard ratio, 1.50). The overall incidence of postoperative complications was similar between the 2 groups. Reoperations for glaucoma were required significantly more frequently in the trabeculectomy group than in the BGI surgery group (20.1 % vs. 5.0%; P0.01).Baerveldt glaucoma implant surgery had a higher success rate compared with trabeculectomy in patients with NVG for a target IOP21 mmHg or17 mmHg. The rates of postoperative complications were similar between both surgical procedures. Additional glaucoma surgery was required more frequently after trabeculectomy than after BGI surgery.

To elucidate the noninferiority of ab interno microhook trabeculotomy (μTLO) using a recently developed reusable stainless spatula-type microhook device to incise the trabecular meshwork to Trabectome (Neomeix, Inc) surgery in terms of the 1-year postoperative outcomes of Japanese patients with glaucoma by means of propensity score analyses.Multicenter, retrospective cohort study.We enrolled 553 and 392 patients who underwent Trabectome surgery and μTLO, respectively, between January 2014 and March 2020 at 10 facilities.Logistic regression analysis was conducted to calculate the propensity score, which indicates the likelihood of treatment assignment (Trabectome or μTLO). We set the following factors as outcome-related covariates: age, sex, facility, glaucoma disease types, preoperative intraocular pressure (IOP), glaucoma drug score, mean deviation of Humphrey visual field test results, antithrombotic drug use, the presence or absence of combined cataract surgery, and incision range of the trabecular meshwork (1 or 2 quadrants). We analyzed 4 different methods (matching, inverse probability of treatment weighting [IPTW], stratification, and regression adjustment) using the propensity score. We set 15% as the noninferiority margin based on previous Trabectome meta-analysis results.The primary outcome was surgical success at 1 year after surgery. We defined surgical success as satisfying all 3 criteria: (1) IOP within 5 to 21 mmHg, (2) IOP reduction of 20% or more from preoperative IOP, and (3) no additional glaucoma surgery.The 95% confidence interval of risk difference of surgical failure in μTLO in reference to Trabectome surgery was -12.1% to +9.5% in matching, -12.7% to +11.1% in IPTW, -12.2 to +7.0 in stratification, and -9.7% to +8.1% in regression adjustment, all of which fell within the predetermined noninferiority margin of 15%.Surgical success of μTLO at 1 year after was not inferior to that of Trabectome surgery.

Aims The Glaucoma Stereo Analysis Study (GSAS) is a multicentre collaborative study of the characteristics of glaucomatous optic disc morphology using a stereo fundus camera. Using the GSAS dataset, we previously established a formula for predicting different appearances of glaucomatous optic discs, although the formula lacked validation in an independent dataset. In this study, the formula was validated in another testing dataset. Subjects and methods Testing dataset contained three-dimensionally analysed optic disc topographic parameters from 93 eyes with primary open-angle glaucoma; six topographic parameters (temporal and nasal rim-disc ratios, mean cup depth, height variation contour, disc tilt angle and rim decentring absolute value) were used for predicting different appearances of glaucomatous optic discs. The agreement between grader-classified optic disc types, that is, focal ischemic (FI), generalized enlargement, myopic glaucomatous (MY), and senile sclerotic (SS) and formula-predicted optic disc types, that is, pFI, pGE, pMY and pSS, were assessed. Results Based on this formula, the eyes were classified with pFI (21 eyes, 22.6%), pGE (27 eyes, 29.0%), pMY (26 eyes, 28.0%) and pSS (19 eyes, 20.4%) when the top predictive element based on the formula was considered as the optic disc appearance in each eye. The six topographic parameters used in the formula differed significantly among the four predicted optic disc types. Substantial agreement (κ = 0.7496) was seen for the top two predictive elements based on the formula that agreed with the graders' classification in 76 (81.7%) eyes. Among the four optic disc types, the levels of agreement were relatively lower in the SS type (κ = 0.3863-0.5729) compared with the other three optic disc types (κ = 0.7898-0.8956) even though the unclassifiable and mixed optic disc types were excluded from the testing dataset. Conclusion The GSAS classification formula can predict and quantify each component of different optic disc appearances in each eye and provide a novel parameter to describe glaucomatous optic disc characteristics.

PRÉCIS: Instillation of brimonidine or timolol slowed visual field deterioration in patients with open-angle glaucoma; both brimonidine and timolol might improve the mean deviation (MD) slopes. PURPOSE: The purpose of this study was to investigate and compare the effects of 0.1% brimonidine and 0.5% timolol on the progressing visual field defects in open-angle glaucoma. PATIENTS AND METHODS: We evaluated 1 eye each of 68 glaucoma patients who were treated with at least 1 prostaglandin analog. Their baseline MD slopes were < −0.5 dB/y based on at least 5 Humphrey field analyzer measurements within 3 years. Eligible eyes were randomly assigned to brimonidine or timolol treatment groups and treatments were administered without the wash-out period. Clinical examinations were performed every 4 months for 2 years. We designated the MD slope as the primary endpoint. RESULTS: Ultimately, 56 eyes (brimonidine:timolol=26:30) were included in the present study (mean age=65.2 y). Dropout rates of brimonidine and timolol treatment groups were 27.8% and 6.3%, respectively. There were no significant differences in baseline intraocular pressure or MD slopes between brimonidine and timolol groups (12.7 and 12.9 mm Hg, P=0.77, and −1.22 and −1.08 dB/y, P=0.43, respectively). Intraocular pressure decreased significantly in the brimonidine group at 4, 8, 12, and 16 months, and in the timolol group at 4 months, without significant differences between the drugs (P=0.20). MD slopes significantly improved in both groups (brimonidine: −0.38 dB/y, P

Purpose: To compare optic nerve head (ONH) blood flow in healthy eyes, eyes with preperimetric glaucoma (PPG), and eyes with mild normal-tension glaucoma (NTG) using laser speckle flowgraphy (LSFG).Methods: In 172 eyes (normal: 44 eyes; PPG: 62 eyes; mild NTG: 66 eyes), LSFG was used to measure mean blur rate in the ONH tissue area (MBRT), an index of capillary blood flow. Multiple regression analysis was performed to determine factors affecting circumpapillary retinal nerve fiber layer thickness (cpRNFLT), mean deviation (MD) and pattern standard deviation (PSD) of the visual field.Results: Despite similar characteristics in age, refractive error and systemic variables among the study groups, MBRT in the normal eyes differed significantly from both the PPG and mild NTG eyes (P = 0.001, P < 0.001, respectively). Multiple regression analysis revealed that MBRT was an independent factor affecting cpRNFLT, MD and PSD (P < 0.001, P = 0.001, P = 0.003, respectively).Conclusion: ONH blood flow was detec...

Purpose The Glaucoma Stereo Analysis Study (GSAS), a cross-sectional multicenter collaborative study, used a stereo fundus camera (nonmyd WX) to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients. We examined the associations between the Disc Damage Likelihood Scale (DDLS), a grading system for estimating glaucomatous ONH damage, and each parameter. Methods The study included 187 eyes of 187 patients with primary open-angle glaucoma or normal-tension glaucoma. ONH morphological parameters including the DDLS stage were calculated with prototype analysis software. Three independent graders classified each optic disc appearance into four different types: focal ischemic, myopic glaucomatous, senile sclerotic, and generalized enlargement. The correlations between the DDLS and patient characteristics or each ONH parameter were analyzed with Spearman’s rank correlation coefficient. Results The DDLS was correlated positively with baseline intraocular pressure and visual field pattern standard deviation, and negatively with visual field mean deviation. The DDLS was strongly correlated with vertical cup-to-disc ratio and horizontal cup-to-disc ratio positively, and with minimum rim-disc ratio negatively. The mean DDLS stage in the myopic glaucomatous type tended to be higher than the scores in other types. Conclusion The DDLS obtained through three-dimensional ONH analysis correlates well with the severity of glaucomatous ONH and visual field damage.

To determine the potential of anterior-segment optical coherence tomography (AS-OCT) to predict posttrabeculectomy outcomes in neovascular glaucoma (NVG).We recruited 45 eyes of 40 NVG patients who underwent trabeculectomy. The patients were divided into success and failure groups based on the posttrabeculectomy outcome after 12 months. AS-OCT findings were compared in the success and failure groups at 1 and 2 weeks and 1, 3, 6, and 12 months. We also analyzed early posttrabeculectomy bleb parameters with multiple logistic regression, stepwise multiple regression, and the receiver operating characteristic curve to evaluate the power of these parameters to predict long-term outcomes.Intraocular pressure at 6 and 12 months was lower in the success group than the failure group (P0.0016=0.0048). Reflectivity of the bleb wall was higher in the failure group than the success group throughout the study (all: P0.0016). Age and reflectivity of the bleb wall at 1 week were risk factors for failure with odds ratios for failure of 0.91 and 1.67. The area under the receiver operating characteristic curve for reflectivity of the bleb wall at 1 week was 0.943 with the cutoff set at 128.9 (sensitivity: 85.7%; specificity: 100.0%). Stepwise multiple regression analysis showed that reflectivity of the bleb wall at 1 week independently indicated the bleb survival period (β=-0.84; P0.001).AS-OCT-measured reflectivity of the bleb wall, measured at 1 week of trabeculectomy for NVG, might be able to predict of the final status of the bleb.

Background/aimsTo investigate the relationship between aqueous flare, visual function and macular structures in retinitis pigmentosa (RP).MethodsClinical data from 123 patients with RP (227 eyes), 35 patients with macular dystrophy (68 eyes) and 148 controls (148 eyes) were analysed. The differences in aqueous flare between clinical entities and the correlation between aqueous flare (measured with a laser flare cell meter) versus visual acuity, visual field area (Goldmann perimetry) and macular thickness (optical coherence tomography) in patients with RP were determined. Influence of selected clinical data on flare was assessed using linear mixed-effects model.ResultsAqueous flare was higher in patients with RP than patients with macular dystrophy or controls (p=7.49×E−13). Aqueous flare was correlated with visual field area (R=−0.379, p=3.72×E−9), but not with visual acuity (R=0.083, p=0.215). Macular thickness (R=0.234, p=3.74×E−4), but not foveal thickness (R=0.122, p=0.067), was positively correlated with flare. Flare was not affected by the presence of macular complications. All these associations were maintained when the right and the left eyes were assessed separately. Analysis by linear mixed-effects model revealed that age (p=8.58×E-5), visual field area (p=8.01×E-7) and average macular thickness (p=0.037) were correlated with flare.ConclusionAqueous flare and visual field area were correlated in patients with RP. Aqueous flare may reflect the degree of overall retinal degeneration more closely than the local foveal impairment.

To determine whether anterior-segment optical coherence tomography (AS-OCT) can be used to predict post-trabeculectomy bleb outcomes.We divided 58 eyes of 47 trabeculectomy patients into success or failure groups based on their status at 12 months after surgery. We then compared various AS-OCT measurement parameters between the two groups at 1 and 2 weeks and 1, 3, 6, and 12 months. We also analyzed the early post-trabeculectomy bleb parameters with multiple logistic regression, stepwise multiple regression, and the receiver operating characteristic (ROC) curve, to evaluate the power of these parameters to predict long-term outcomes.Intraocular pressure 3 or more months after trabeculectomy was significantly lower in the success group than the failure group (all: P 0.0016). Cleft volume was significantly higher 6 or more months after trabeculectomy in the success group than the failure group (P = 0.0027 and0.0016). Reflectivity of the bleb wall was significantly higher in the failure group than the success group at 2 weeks and all later time points (all: P 0.0016). Reflectivity of the bleb wall at 2 weeks after trabeculectomy was a risk factor for failure, with an odds ratio (OR) for failure of 2.48 (95% confidence interval, 1.31-4.68, increasing per 10 AU). The area under the ROC curve for reflectivity of the bleb wall at 2 weeks after trabeculectomy was 0.775 when the cutoff value was set at 122.8, with sensitivity, specificity, and OR of 78.3%, 80.0%, and 14.4, respectively. A stepwise multiple regression analysis showed that reflectivity of the bleb wall at 2 weeks was an independent factor indicating postoperative bleb survival period (β = -0.39, P = 0.007).Reflectivity of the bleb wall, measured by AS-OCT, may be an early post-trabeculectomy predictor of bleb outcome.

Optic nerve crush (ONC) and subsequent axonal damage can be used in rodents to study the mechanism of retinal ganglion cell (RGC) degeneration. Here, we examined electroretinograms (ERGs) in post-ONC mice to investigate changes in the positive scotopic threshold response (pSTR). We then compared these changes with molecular and morphological changes to identify early objective biomarkers of RGC dysfunction.Fifty 12-week-old C57BL/6 mice were included. ONC was used to induce axonal injury in the right eye of each animal, with the left eye used as a control. The expression of the RGC markers Brn3a and Brn3b was measured on days 1, 2, 3, 5 and 7 after ONC with quantitative real-time PCR. ERGs were recorded under dark adaptation with the stimulus intensity increasing from -6.2 to 0.43 log cd-s/m(2) on days 1, 2, 3, 5, 7 and 10 after ONC. The pSTR, a- and b-wave amplitudes were measured. Inner retinal thickness around the optic nerve head was measured with spectral-domain optical coherence tomography on days 0, 2, 5, 7 and 10 after ONC.The expression of Brn3a and Brn3b began to significantly decrease on day 1 and day 2, respectively (P 0.01). The amplitude of the pSTR underwent rapid, significant deterioration on day 3, after which it fell gradually (P 0.01), while the a- and b-wave amplitudes remained unchanged throughout the experiment. Inner retinal thickness gradually decreased, with the most significant reduction on day 10 (P 0.01).Decrease in pSTR likely reflected the early loss of RGC function after ONC and that declining expression of RGC-specific genes preceded anatomical and functional changes in the RGCs.

Purpose. The Glaucoma Stereo Analysis Study, a cross-sectional multicenter collaborative study, used a stereo fundus camera (nonmyd WX) to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients. We compared the associations of each parameter between the visual field loss progression group and no-progression group. Methods. The study included 187 eyes of 187 patients with primary open-angle glaucoma or normal-tension glaucoma. We divided the mean deviation (MD) slope values of all patients into the progression group (Results. The MD slope averages in the progression group and no-progression group were −0.58 ± 0.28 dB/year and 0.05 ± 0.26 dB/year, respectively. Among disc parameters, vertical disc width (diameter), disc area, cup area, and cup volume in the progression group were significantly less than those in the no-progression group. Logistic regression analysis revealed a significant association between the visual field progression and disc area (odds ratio 0.49/mm2 disc area). Conclusion. A smaller disc area may be associated with more rapid glaucomatous visual field progression.

PURPOSE To identify sectors of the optical coherence tomography (OCT) macular map that could be used to effectively assess structural progression in patients with normal-tension glaucoma (NTG). METHODS This study examined 117 eyes of 117 NTG patients to establish axonal tract-dependent macular sectors, and also examined a separate group of 122 eyes of 81 NTG patients to evaluate the ability of these sectors to reveal glaucoma progression. Longitudinal data, including macular maps from at least 5 OCT examinations performed over at least 2 years, was available for all patients in this group. Circumpapillary retinal nerve fiber layer thickness (cpRNFLT), temporal clockwise sector scans (from 7 to 11 o'clock), macular retinal nerve fiber layer thickness (mRNFLT), and macular ganglion cell layer plus inner plexiform layer thickness (mGCIPLT) were measured with spectral-domain OCT (3D OCT-2000, TOPCON). The axonal tract-dependent macular sectors were identified by calculating Spearman's rank correlation coefficient for each point on a grid overlaid on the macular map and cpRNFLT in each clockwise scan sector. Trend and event analyses for the slope of progression in each sector and macular map were performed. Visual field progression in the macula was defined by the presence of more than 2 progressive test points in the 16 central test points of the Humphrey field analyzer SITA standard 24-2 program, evaluated with Progressor software. RESULTS The slope of progression in the entire macular area was -0.22 ± 0.58 μm/year for mRNFLT and -0.35 ± 0.52 μm/year for mGCIPLT. The fastest-progressing mRNFLT sector (-1.00 ± 0.84 μm/year, p < 0.001) and mGCIPLT sector (-1.16 ± 0.63 μm/year, p < 0.001) progressed significantly faster than the overall macula. Classifying patients according to visual field progression showed that baseline mRNFLT in the inferior hemifield, 7 and 8 o'clock sectors, as well as baseline mGCIPLT in the overall macular map, inferior hemifield, and 8 o'clock sector, were significantly lower in progressors (22 eyes) than non-progressors (100 eyes). There were significant differences in mRNFLT slope in 8 o'clock sector and in the fastest progressing sector in progressors and non-progressors, but mGCIPLT did not differ, even in the fastest-progressing sector. Event analysis showed that progression occurred most frequently in inferior mRNFLT and superior mGCIPLT in this study. CONCLUSION Axonal tract-dependent OCT macular sectors could effectively reveal structural change in patients with NTG. Furthermore, mRNFLT slope was consistent with visual field progression. This method promises to open new avenues for the OCT-based evaluation of glaucoma progression.

We report observations of very low frequency (VLF) and extremely low frequency (ELF) chorus waves taken during the ELF/VLF Campaign observation with High-resolution Aurora Imaging Network (VLF-CHAIN) of 17–25 February 2012 at subauroral latitudes at Athabasca (L=4.3), Canada. ELF/VLF waves were measured continuously with a sampling rate of 100 kHz to monitor daily variations in ELF/VLF emissions and derive their detailed structures. We found quasiperiodic (QP) emissions whose repetition period changes rapidly within a period of 1 h without corresponding magnetic pulsations. QP emissions showed positive correlation between amplitude and frequency sweep rate, similarly to rising-tone elements. We found an event of nearly simultaneous enhancements of QP emissions and Pc1/electromagnetic ion cyclotron wave intensities, suggesting that the temperature anisotropy of electrons and ions developed simultaneously at the equatorial plane of the magnetosphere. We also found QP emissions whose intensity suddenly increased in association with storm sudden commencement without changing their frequency. Falling-tone ELF/VLF emissions were observed with their rate of frequency change varying from 0.7 to 0.05 kHz/s over 10 min. Bursty-patch emissions in the lower and upper frequency bands are often observed during magnetically disturbed periods. Clear systematic correlation between these various ELF/VLF emissions and cosmic noise absorption was not obtained throughout the campaign period. These observations indicate several previously unknown features of ELF/VLF emissions in subauroral latitudes and demonstrate the importance of continuous measurements for monitoring temporal variations in these emissions.

In this study, we set out to establish an in vivo animal model of oxidative stress in the retinal ganglion cells (RGCs) and determine whether there is a link between oxidative stress in the RGCs and the activation of calpain, a major part of the apoptotic pathway.Oxidative stress was induced in the RGCs of C57BL/6 mice by the intravitreal administration of 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH, 30mM, 2μl). Control eyes were injected with 2μl of vehicle. Surviving Fluorogold (FG)-labeled RGCs were then counted in retinal flat mounts. Double staining with CellROX and Annexin V was performed to investigate the co-localization of free radical generation and apoptosis. An immunoblot assay was used both to indirectly evaluate calpain activation in the AAPH-treated eyes by confirming α-fodrin cleavage, and also to evaluate the effect of SNJ-1945 (a specific calpain inhibitor: 4% w/v, 100mg/kg, intraperitoneal administration) in these eyes.Intravitreal administration of AAPH led to a significant decrease in FG-labeled RGCs 7days after treatment (control: 3806.7±575.2RGCs/mm(2), AAPH: 3156.1±371.2RGCs/mm(2), P0.01). CellROX and Annexin V signals were co-localized in the FG-labeled RGCs 24h after AAPH injection. An immunoblot assay revealed a cleaved α-fodrin band that increased significantly 24h after AAPH administration. Intraperitoneally administered SNJ-1945 prevented the cleavage of α-fodrin and had a neuroprotective effect against AAPH-induced RGC death (AAPH: 3354.0±226.9RGCs/mm(2), AAPH+SNJ-1945: 3717.1±614.6RGCs/mm(2), P0.01).AAPH administration was an effective model of oxidative stress in the RGCs, showing that oxidative stress directly activated the calpain pathway and induced RGC death. Furthermore, inhibition of the calpain pathway protected the RGCs after AAPH administration.

Artemin, a recently discovered member of the glial cell line-derived neurotrophic factor (GDNF) family, has neurotrophic effects on damaged neurons, including sympathetic neurons, dopamine neurons, and spiral ganglion neurons both in vivo and in vitro. However, its effects on retinal cells and its intracellular signaling remain relatively unexplored. During development, expression of GFRα3, a specific receptor for artemin, is strong in the immature retina and gradually decreases during maturation, suggesting a possible role in the formation of retinal connections. Optic nerve damage in mature rats causes levels of GFRα3 mRNA to increase tenfold in the retina within 3 days. GFRα3 mRNA levels continue to rise within the first week and then decline. Artemin, a specific ligand for GFRα3, has a neuroprotective effect on axotomized retinal ganglion cells (RGCs) in vivo and in vitro via activation of the extracellular signal-related kinase- and phosphoinositide 3-kinase-Akt signaling pathways. Artemin also has a substantial effect on axon regeneration in RGCs both in vivo and in vitro, whereas other GDNF family members do not. Therefore, artemin/GFRα3, but not other GDNF family members, may be of value for optic nerve regeneration in mature mammals.

To explore methods of automated visual field (VF) examination for the assessment of macular function.We used a VF examination (AP-7000 automatic perimeter, Kowa, Japan) to examine macular function in 53 eyes from 29 patients with open angle glaucoma. We measured the mean total deviation (c-MD) of 16 points in the central VF located in a 2-degree-interval 4 × 4 array with various stimulus sizes (Goldmann sizes III, II, and I). The retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC), and ganglion cell layer plus inner plexiform layer (GCL + IPL) were measured with the 3D OCT-2000 System (Topcon, Japan). The c-MDs of various stimulus sizes were compared with the OCT parameters using the Spearman rank correlation.The average examination time was 93.5 ± 23.5 s and the c-MD values were -11.8 ± 8.2 (stimulus size III), -11.9 ± 9.5 (stimulus size II), and -12.3 ± 9.6 dB (stimulus size I). The c-MD (stimulus size III) and averaged total deviations of the Humphrey Field Analysis 10-2 program were significantly correlated (ρ = 0.91). The C-MD values for stimulus size III were significantly correlated with the OCT parameters (RNFL: ρ = 0.59; GCC: ρ = 0.65; and GCL + IPL: ρ = 0.64). The correlation coefficient between the c-MD and the GCC was better for stimulus sizes II and I (ρ = 0.69) than for stimulus size III (ρ = 0.65).The C-MD values for the 16 measured central VF points were significantly correlated with macular structure, and the smaller stimulus sizes of the automated VF test had a higher correlation coefficient of within 8°.

To investigate, using laser speckle flowgraphy (LSFG), the autoregulation of ocular blood flow (BF) in response to posture change.This study comprised 20 healthy volunteers (mean age 30.0 ± 8.5). The mean blur rate (MBR) of the ocular circulation in the subjects was assessed in both a sitting and a supine position every 2 min over the course of 10 min. Baseline measurements of the MBR at the optic nerve head (ONH) and the choroid were taken in a sitting position. Increases in the MBR ratio in a supine position were calculated with reference to this baseline. Intraocular pressure (IOP), systemic blood pressure and heart rate in the brachial artery were also recorded.In the ONH, the MBR ratio increased significantly over the baseline after 2 min (104.8 ± 5.0%, p = 0.001) and 4 min (104.4 ± 5.6%, p = 0.005), in a supine position, but decreased to the initial level after only 6 min. In the choroid, on the other hand, while the MBR ratio also increased significantly after 2 min in a supine position (113.7 ± 8.1%, p0.001), it kept this significant increase over the time course of 10 min. After 10 min in a supine position, IOP increased significantly (p0.001), systolic blood pressure decreased significantly (p0.001), but diastolic blood pressure did not change significantly compared to the baseline. (p = 0.07) CONCLUSIONS: ONH and choroidal circulation have significantly different hemodynamics in response to posture change in healthy volunteers. This finding suggests that LSFG enables us to assess the autoregulation of BF in the ONH.

Scientific reports 7(1), 6564 (2017). doi:10.1038/s41598-017-06890-w, Through high-energy x-ray diffraction and atomic pair density function analysis we find that Zr-based metallic alloy, heated to the supercooled liquid state under hydrostatic pressure and then quenched to room temperature, exhibits a distinct glassy structure. The PDF indicates that the Zr-Zr distances in this glass are significantly reduced compared to those quenched without pressure. Annealing at the glass transition temperature at ambient pressure reverses structural changes and the initial glassy state is recovered. This result suggests that pressure causes a liquid-to-liquid phase transition in this metallic alloy supercooled melt. Such a pressure induced transition is known for covalent liquids, but has not been observed for metallic liquids. The High Pressure Quenched glasses are stable in ambient conditions after decompression., Published by Nature Publishing Group, London

PURPOSE To investigate the effect of topical tafluprost on optic disc blood flow in patients with myopic disc. MATERIALS AND METHODS Forty-eight eyes in 24 patients with a myopic disc type (oval shaped) optic disc tilted to the temporal, with a crescent peripapillary atrophy were included in this study. Twenty-eight eyes were diagnosed as normal tension glaucoma and 20 eyes were in normal subjects. None had any treatment for glaucoma. Average age was 45.3±11.9 years. One eye was treated with topical tafluprost and the fellow eye served as the control. Ocular blood flow was measured by laser speckle flowgraphy (LSFG-NAVI) at 30, 60, 90, and 120 minutes after tafluprost administration, and the mean blur rate (MBR) on the optic disc was analyzed. Blood pressure and intraocular pressure (IOP) were recorded. RESULTS In all subjects, topical tafluprost (a) significantly reduced IOP versus baseline from 60 minutes after treatment (baseline: 15.2±3.4 mm Hg, 60 min: 13.3±3.2 mm Hg, P=0.001, 90 min: 13.3±3.6 mm Hg, P=0.002, 120 min: 13.7±3.4 mm Hg, P=0.007); and (b) significantly increased the MBR versus baseline (60 min: +4.3±6.6%, P=0.008, 90 min: +5.0±4.9%, P

The Glaucoma Stereo Analysis Study (GSAS) is a multicenter collaborative study of the characteristics of glaucomatous optic disc morphology using a stereo fundus camera. Using GSAS dataset, the formulas for predicting different glaucomatous optic disc appearances were established. The GSAS dataset containing three-dimensionally-analyzed optic disc topographic parameters from 187 eyes with primary open-angle glaucoma was assessed with discrimination analyses to obtain formulas predictive of glaucomatous optic disc appearances: focal ischemic (FI); generalized enlargement (GE), myopic glaucomatous (MY), and senile sclerotic (SS). Using 38 optic disc parameters-substituted discrimination analyses with a stepwise forward-selection method, six parameters (temporal and nasal rim-disc ratios, mean cup depth, height variation contour, disc tilt angle, and rim decentering absolute) were selected into the formulas. The area under the receiver operating characteristic curves for predicting the four disc types with established formulas were 0.88, 0.91, 0.93, and 0.86 for FI, MY, SS, and GE, respectively. Age, visual acuity, refractive error, glaucoma (normal or high-tension glaucoma), and baseline intraocular pressure differed significantly among the four optic disc types, suggesting the appearances represent different clinical glaucoma phenotypes. Using six optic disc topographic parameters obtained by stereo fundus camera, the GSAS classification formulas predicted and quantified each component of different optic disc appearances in each eye and provided a novel parameter to describe glaucomatous optic disc characteristics.

Calpain, an intracellular cysteine protease, has been widely reported to be involved in neuronal cell death. The purpose of this study is to investigate the role of calpain activation in axonal damage-induced retinal ganglion cell (RGC) death. Twelve-week-old male calpstatin (an endogenous calpain inhibitor) knockout mice (CAST KO) and wild-type (WT) mice were used in this study. Axonal damage was induced by optic nerve crush (NC) or tubulin destruction induced by leaving a gelatin sponge soaked with vinblastine (VB), a microtubule disassembly chemical, around the optic nerve. Calpain activation was assessed by immunoblot analysis, which indirectly quantified the cleaved α-fodrin, a substrate of calpain. RGCs were retrogradely labeled by injecting a fluorescent tracer, Fluoro-Gold (FG), and the retinas were harvested and flat-mounted retinas prepared. The densities of FG-labeled RGCs harvested from the WT and CAST KO groups were assessed and compared. Additionally, a calpain inhibitor (SNJ-1945, 100 mg/kg/day) was administered orally, and the density of surviving RGCs was compared with that of the vehicle control group. The mean density of surviving RGCs in the CAST KO group was significantly lower than that observed in the WT group, both in NC and in VB. The mean density of surviving RGCs in the SNJ-1945-treated group was significantly higher than that of the control group. The calpain inhibitor SNJ-1945 has a neuroprotective effect against axonal damage-induced RGC death. This pathway may be an important therapeutic target for preventing this axonal damage-induced RGC death, including glaucoma and diabetic optic neuropathy and other CNS diseases that share a common etiology.

Purpose To objectively classify the optic discs of open-angle glaucoma (OAG) patients into Nicolela's four disc types, i.e., focal ischemic (FI), myopic (MY), senile sclerotic (SS), and generalized enlargement (GE), with swept-source optical coherence tomography (SS-OCT). Methods This study enrolled 113 eyes of 113 OAG patients (mean age: 62.5 ± 12.6; Humphrey field analyzer-measured mean deviation: -9.4 ± 7.3 dB). Newly developed software was used to quantify a total of 20 optic disc parameters in SS-OCT (DRI OCT-1, TOPCON) images of the optic disc. The most suitable reference plane (RP) above the plane of Bruch’s membrane opening was determined by comparing, at various RP heights, the SS-OCT-measured rim parameters and spectral-domain OCT-measured circumpapillary retinal nerve fiber layer thickness (cpRNFLT), with Pearson's correlation analysis. To obtain a discriminant formula for disc type classification, a training group of 72 eyes of 72 OAG patients and a validation group of 60 eyes of 60 OAG patients were set up. Results Correlation with cpRNFLT differed with disc type and RP height, but overall, a height of 120 μm minimized the influence of disc type. Six parameters were most significant for disc type discrimination: disc angle (horizontal), average cup depth, cup/disc ratio, rim-decentering ratio, average rim/disc ratio (upper and lower nasal). Classifying the validation group with these parameters returned an identification rate of 80.0% and a Cohen’s Kappa of 0.73. Conclusion Our new, objective SS-OCT-based method enabled us to classify glaucomatous optic discs with high reproducibility and accuracy.

Purpose To ascertain the association between fundus drusens and biological parameters in a colony of 1174 monkeys. Methods Presence or absence of drusens was determined through the assessment of fundus photos taken during 2011 – 2013 from 1,174 Macaca fascicularis at Tsukuba Primate Research Center. Biological data from these monkeys including blood test result, age, sex, and body weight were tested for an association between the presence of drusens by applying t-test and logistic regression analysis. Results We identified 387 and 787 monkeys with and without drusens, respectively. Among them, 317 and 628 monkeys with and without drusens that had a complete biological data set were further studied. After comparing each parameter in monkeys with and without drusens, 13 factors with a significance of P

Glaucoma, a leading cause of blindness worldwide, is instigated by various factors, including axonal injury, which eventually leads to a progressive loss of retinal ganglion cells (RGCs). To study various pathways reportedly involved in the pathogenesis of RGC death caused by axonal injury, seven pathways were investigated. Pathway-specific fluorescent protein-coded reporters were each packaged into an adeno-associated virus (AAV). After producing axonal injury in the eye, injected with AAV to induce RGC death, the temporal activity of each stress-related pathway was monitored in vivo through the detection of fluorescent RGCs using confocal ophthalmoscopy. We identified the activation of ATF6 and MCP-1 pathways involved in endoplasmic reticulum stress and macrophage recruitment, respectively, as early markers of RGC stress that precede neuronal death. Conversely, inflammatory responses probed by NF-κB and cell-death-related pathway p53 were most prominent in the later phases, when RGC death was already ongoing. AAV-mediated delivery of stress/response reporters followed by in vivo cellular imaging is a powerful strategy to characterize the temporal aspects of complex molecular pathways involved in retinal diseases. The identification of promoter elements that are activated before the death of RGCs enables the development of pre-emptive gene therapy, exclusively targeting the early phases of diseased cells.