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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.

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.

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.

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.

Purpose There is no consensus on the diagnosis or treatment policy for Preperimetric Glaucoma (PPG) because the pathogenesis of PPG is not clear at this time. Preperimetric Glaucoma Prospective Observational Study (PPGPS) is a first multicenter, prospective, observational study to clarify the pathogenesis of PPG. This article indicates study design, patient baseline characteristics, and analysis focused on optic nerve head (ONH) blood flow in PPG, as well as the intraocular pressure (IOP) -lowering effect and ONH blood flow-improving effects of Tafluprost. Method In this study, 122 eyes from 122 subjects (mean age: 53.1 ± 14.3) newly diagnosed as PPG were enrolled. The circumpapillary retinal nerve fiber layer thickness (cpRNFLT) was evaluated with optical coherence tomography (OCT). The ONH blood flow was measured with laser speckle flowgraphy. The therapeutic effect of Tafluprost was evaluated at Month 0 (ONH blood flow-improving effect) and Month 4 (IOP-lowering effect). Results The untreated IOP, cpRNFLT, and baseline Mean deviation (MD) value was 16.4 ± 2.5 mmHg, 80.4 ± 8.2 μm, and -0.48 ± 1.29 dB, respectively. In the site-specific visual field evaluation using the sector map, there was no appreciable site-specific visual field defect in the eye with PPG. The inferior region of cpRNFLT in 4-quadrant OCT sector analysis and 6 o’clock region in 12-o’clock OCT sector analysis was the highest rate of abnormality in PPG eyes. Topical administration of Tafluprost significantly reduced IOP from 16.4 ± 2.5 mmHg at baseline to 14.5 ± 2.3 mmHg at Month 4 (P < 0.001, paired t-test). In the linear regression analysis, there was a significant relationship between the increase of ONH blood flow and baseline value. Conclusion PPGPS is a first prospective study focusing on the pathology of PPG. This study is expected to elucidate the pathology of PPG, with evidence useful for determining a treatment strategy for PPG.

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.

Kazuko Omodaka, Toru Nakazawa, Yu Yokoyama, Hiroshi Doi, Nobuo Fuse, Kohji NishidaDepartment of Ophthalmology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Miyagi, JapanPurpose: To determine whether the best-corrected visual acuity (BCVA) is significantly correlated with the retinal nerve fiber layer thickness (RNFLT) in the different peripapillary areas in eyes with open-angle glaucoma (OAG).Patients and methods: Two hundred twenty-nine eyes of 159 patients with OAG were studied. The overall RNFLT and the RNFLT in the superior (S), temporal (T), inferior (I), and nasal (N) quadrants were measured by Stratus optical coherence tomography (OCT). In addition, the temporal RNFLT was measured for three 30° sectors with the mid-temporal (mT) sector at the three or nine o’clock position. The Spearman coefficient of correlation was calculated to determine whether a significant correlation existed between the RNFLT and the BCVA. Eyes with a BCVA < 20/20 were classified as having decreased BCVA. Results: There were significant correlations between the BCVA and the overall RNFLT, andalso between the BCVA and the RNFLT in the T, I, and S quadrants. The coefficient correlation between the BCVA and RNFLT was the highest in the mT sector (r = −0.40, P < 0.0001). Forty-eight eyes (21.1%) were classified as having decreased BCVA. The cut-off value of the mT sector for eyes with decreased VA was 39.0 μm.Conclusion: The highest correlation between the BCVA and the RNFLT in the mT sector was most likely due to the location of the maculopapillary bundle in this region of the optic disc. Our findings indicate that when the RNFLT in the mT sector is reduced to 40 μm, glaucoma treatment should be reconsidered.Keywords: retinal nerve fiber layer, low vision, peripapillary macular bundle

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.

The retinal ganglion cells (RGCs) are the main source of therapeutic targets for neuroprotective glaucoma treatment, and evaluating RGCs is key for effective glaucoma care. Thus, we developed a minimally invasive, quick, real-time method to evaluate RGC death in mice. In this article we describe the details of our method, report new results obtained from C57BL/6J mice, and report that our method was usable in wild type (WT) and knockout (KO) mice lacking an RGC-death-suppressing gene. It used a non-invasive confocal scanning laser ophthalmoscope (cSLO) and a low molecular weight, photo-switching, cell-impermeant, fluorescent nucleic acid dyeing compound, SYTOX orange (SO). The RGCs were retrogradely labeled with Fluorogold (FG), the optic nerve was crushed (ONC), and SO was injected into the vitreous. After ten minutes, RGC death was visualized with cSLO in vivo. The retinas were then extracted and flat mounted for histological observation. SO-labeled RGCs were counted in vivo and FG-labeled RGCs were counted in retinal flat mounts. The time course of RGC death was examined in Calpastatin KO mice and wild type (WT) mice. Our in vivo imaging method revealed that SO-positive dead RGCs were mainly present from 4 to 6 days after ONC, and the peak of RGC death was after 5 days. Moreover, the number of SO-positive dead RGCs after 5 days differed significantly in the Calpastatin KO mice and the WT mice. Counting FG-labeled RGCs in isolated retinas confirmed these results. Thus, real-time imaging with SO was able to quickly quantify ONC-induced RGC death. This technique may aid research into RGC death and the development of new neuroprotective therapies for glaucoma.

Purpose To investigate the site specificity of visual field changes in eyes with normotensive preperimetric glaucoma (PPG), and to determine factors influencing visual field progression. Methods This prospective study comprised 84 eyes of 84 normotensive PPG patients followed for at least 16 months. Optic nerve head (ONH) blood flow was assessed with tissue-area mean blur rate (MBRT), derived from laser speckle flowgraphy. Total deviation (TD) was measured in each sector of the Garway-Heath map to evaluate the site specificity of visual field loss. Subjects with a TD slope in the first quartile were classified as progressive, and other subjects as nonprogressive. Linear and multiple regression analyses were performed to determine factors affecting visual field progression. Results TD in the superior sector significantly decreased in the subjects overall during the follow-up periods (-0.48 ± 1.92 dB/y, P = 0.025). Linear regression analysis showed that basal MBRT-inferior was correlated significantly with TD-superior slope (r = 0.332, P = 0.002). Furthermore, basal MBRT was significantly lower in this sector in the progressive than the nonprogressive group (P = 0.010). Multiple linear regression analysis revealed that basal MBRT-inferior was the only predictive factor for TD-superior slope (β = 0.329, P = 0.005). Conclusions These findings suggest that superior-sector visual field progression is most common in normotensive PPG eyes, and that reduced basal ONH blood flow is associated with visual field progression. Translational relevance These findings provide new insight into the involvement of ONH blood flow impairment in glaucoma pathogenesis, and demonstrate the importance of assessing ONH blood flow to determine visual field progression in normotensive PPG.

We demonstrate a prototype system of polarization-sensitive optical coherence tomography (PS-OCT) designed for clinical studies of the anterior eye segment imaging. The system can measure Jones matrices of the sample with depth-multiplexing of two orthogonal incident polarizations and polarization-sensitive detection. An optical clock is generated using a quadrature modulator and a logical circuit to double the clock frequency. Systematic artifacts in measured Jones matrices are theoretically analyzed and numerically compensated using signals at the surface of the sample. Local retardation images of filtering blebs after trabeculectomy show improved visualization of subconjunctival tissue, sclera, and scar tissue of the bleb wall in the anterior eye segment.

Among various risk factors for the pathogenesis of glaucoma, intraocular pressure has been identified as playing a causative role in the process of axonal degeneration, and at present, it remains the only risk factor considered in glaucoma treatment. However, epidemiology studies have also shown that myopia is a risk factor for glaucoma, especially for normal tension glaucoma. Myopia is more common in Asia than in Western countries, and normal tension glaucoma is the most common type of open angle glaucoma in Asia. Normal tension glaucoma often causes central visual field loss, which can directly influence quality of life in patients.

To define topographical areas of the macula in optical coherence tomography (OCT) scans by identifying regions in which macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (mGCL + IPL) thickness was highly correlated with clockwise circumpapillary RNFL (cpRNFL) thickness in patients with normal tension glaucoma (NTG).This study included 101 eyes of 101 patients with mild or moderate NTG. CpRNFL, mRNFL, and mGCL + IPL thickness were assessed with spectral-domain OCT (3D OCT-2000). The region of interest (6 × 6 mm square) was centered on the fovea and layer thickness was measured at each point on a 10 × 10 grid. Spearman's rank correlation coefficient was determined between each temporal clockwise sector (7, 8, 9, 10, 11 o'clock) of the cpRNFL and each grid point in the mRNFL and mGCL + IPL. Grid points were defined as correlated to specific clockwise sectors when the correlation coefficient was more than 0.4. To validate the areas comprised by these points, they were superimposed on a swept-source OCT image (12 × 9 mm, EnView software, Topcon) showing the anatomical trajectory of nerve fiber defects.Macular areas with a high correlation coefficient (r ≥ 0.4, p 0.05) to clockwise cpRNFL were identified. The number of grid points in the mRNFL and mGCL + IPL correlated to specific clockwise cpRNFL sectors was, respectively, 40 and 18 (7 o'clock), 41 and 22 (8), 33 and 44 (9), 39 and 39 (10), and 18 and 19 (11) (r = 0.40-0.79). Interestingly, the distribution of mRNFL sectors closely matched the RNFL defects in the OCT image, although the mGCL + IPL sectors differed and were closer to the fovea than the mRNFL sectors.The identification of these topographical macular areas, and the different layouts in the mRNFL and the mGCL + IPL, may increase the accuracy of clinical research on NTG.

Background It is difficult to identify glaucoma in myopic eyes because the configuration of the optic disc varies; yet it is important clinically. Here, we used laser speckle flowgraphy (LSFG) to measure mean blur rate (MBR), representing optic disc microcirculation, and assessed its ability to identify glaucoma in eyes with myopic optic discs. Methods 129 eyes (normal disc: 21 eyes; myopic disc: 108 eyes) were enrolled. The eyes were classified as normal or mildly, moderately, or severely glaucomatous with standard automated perimetry (SAP). We determined the relationship between optic nerve head (ONH) MBR, measured with LSFG, mean deviation (MD), measured with SAP, and circumpapillary retinal nerve fiber layer thickness (cpRNFLT), measured with optical coherence tomography (OCT). Results ONH MBR and cpRNFLT decreased significantly with the severity of glaucoma. MBR was significantly correlated with cpRNFLT and MD (r =0.65 and r =0.63, respectively). A multiple regression analysis revealed that MBR and cpRNFLT were independent factors indicating glaucoma severity. A logistic regression analysis revealed that MBR and cpRNFLT were also independent factors indicating the presence of glaucoma. In a receiver operating characteristic (ROC) analysis, MBR and cpRNFLT could both differentiate between normal and glaucomatous eyes (MBR area under the ROC curve: 0.86, with a cut-off score of 24.0 AU). Conclusion These results suggest that in addition to cpRNFLT, non-invasive and objective LSFG measurements of MBR may enable the identification of glaucoma and the classification of its severity in eyes with myopic optic discs.

Purpose: The Glaucoma Stereo Analysis Study (GSAS), a cross sectional multicenter collaborative study, used a stereo fundus camera to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients and investigated the relationships between these parameters and patient characteristics. Subjects and Methods: The study included 187 eyes of 187 subjects with primary open angle glaucoma or normal tension glaucoma (male: female =100: 87, age =6169 years). Stereo pairs of ONH photographs were made with a stereo fundus camera (nonmyd WX). ONH morphological parameters were calculated with prototype analysis software. In addition to 35 standard parameters, we defined three novel parameters: disc tilt angle, rim decentering, and the absolute value of rim decentering. The correlation between each parameter and patient characteristics was analyzed with Spearman’s rank correlation coefficient. Results: Patient characteristics included refractive error of 23.3863.75 diopters, intraocular pressure (IOP) of 13.662.6 mmHg, and visual field mean deviation (MD) of 24.7163.26 dB. Representative ONH parameters included a horizontal disc width of 1.6660.28 mm, vertical disc width of 1.8660.23 mm, disc area of 2.4260.63 mm 2 , cup area of 1.4560.57 mm 2 , and cup volume of 0.3160.22 mm 3 . Correlation analysis revealed significant negative associations between vertical cup-to-disc ratio (0.8260.08) and MD (r= 20.40, P,0.01) and between disc tilt angle (10.5612.5 degrees) and refractive error (r= 20.36, P,0.01). Seventy-five percent of the eyes had a positive value for rim decentering (0.3060.42), indicating that rim thinning manifested more often as an inferior lesion than a superior lesion. Conclusion: We used stereoscopic analysis to establish a database of ONH parameters, which may facilitate future studies of glaucomatous changes in ONH morphology.

Age-dependent formation of macular drusen caused by the focal accumulation of extracellular deposits beneath the retinal pigment epithelium precede the development of age-related macular degeneration (AMD), one of the leading causes of blindness worldwide. It is established that inflammation contributes to the pathogenesis of drusen and AMD. However, development of a preemptive therapeutic strategy targeting macular drusen and AMD has been impeded by the lack of relevant animal models because most laboratory animals lack macula, an anatomic feature present only in humans and a subset of monkeys. Reportedly, macular drusen and macular degeneration develop in monkeys in an age-dependent manner. In this study, we analyzed blood test results from 945 Macaca fascicularis, 317 with and 628 without drusen. First, a trend test for drusen frequency (the Cochran-Armitage test) was applied to the quartile data for each parameter. We selected variables with an increasing or decreasing trend with higher quartiles at P < 0.05, to which multivariate logistic regression analysis was applied. This revealed a positive association of age (odds ratio [OR]: 1.10 per year, 95% confidence interval [CI]: 1.07-1.12) and white blood cell count (OR: 1.01 per 1 × 103/μl, 95% CI: 1.00-1.01) with drusen. When the monkeys were divided by age, the association between drusen and white blood cell count was only evident in younger monkeys (OR: 1.01 per 1 × 103/μl, 95% CI: 1.00-1.02). In conclusion, age and white blood cell count may be associated with drusen development in M. fascicularis. Systemic inflammation may contribute to drusen formation in monkeys.

Yu Yokoyama, Naoko Aizawa, Naoki Chiba, Kazuko Omodaka, Masahiko Nakamura, Takaaki Otomo, Shunji Yokokura, Nobuo Fuse, Toru NakazawaDepartment of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, JapanBackground: Eyes with glaucoma are characterized by optic neuropathy with visual field defects in the areas corresponding to the optic disk damage. The exact cause for the glaucomatous optic neuropathy has not been determined. Myopia has been shown to be a risk factor for glaucoma. The purpose of this study was to determine whether a significant correlation existed between the microcirculation of the optic disk and the visual field defects and the retinal nerve fiber layer thickness (RNFLT) in glaucoma patients with myopic optic disks.Methods: Sixty eyes of 60 patients with myopic disks were studied; 36 eyes with glaucoma (men:women = 19:17) and 24 eyes with no ocular diseases (men:women = 14:10). The mean deviation (MD) determined by the Humphrey field analyzer, and the peripapillary RNFLT determined by the Stratus-OCT were compared between the two groups. The ocular circulation was determined by laser speckle flowgraphy (LSFG), and the mean blur rate (MBR) was compared between the two groups. The correlations between the RNFLT and MBR of the corresponding areas of the optic disk and between MD and MBR of the optic disk in the glaucoma group were determined by simple regression analyses.Results: The average MBR for the entire optic disk was significantly lower in the glaucoma group than that in the control group. The differences of the MBR for the tissue in the superior, inferior, and temporal quadrants of the optic disk between the two groups were significant. The MBR for the entire optic disk was significantly correlated with the MD (r = 0.58, P = 0.0002) and the average RNFLT (r = 0.53, P = 0.0008). The tissue MBR of the optic disk was significantly correlated with the RNFLT in the superior, inferior, and temporal quadrants.Conclusions: Our study suggests that there is a causal relationship between the thinner RNFLT that led to the MD and reduction in the microcirculation in the optic nerve head.Keywords: glaucoma, visual field defects, optic disk, optic neuropathy, myopia, microcirculation, optic nerve head, retinal nerve fiber layer

Naoko Aizawa, Yu Yokoyama, Naoki Chiba, Kazuko Omodaka, Masayuki Yasuda, Takaaki Otomo, Masahiko Nakamura, Nobuo Fuse, Toru NakazawaDepartment of Ophthalmology, Tohoku University Graduate School of Medicine Sendai, Miyagi, JapanBackground: Laser speckle flowgraphy (LSFG) enables noninvasive quantification of the retinal circulation in glaucoma patients. In this study, we tested the intrasession reproducibility of LSFG-NAVI, a modified LSFG technique.Methods: Sixty-five eyes from 33 subjects (male (M):female (F) = 17:16) with a mean age of 49.4 ± 11.2 years were examined in this study. Two parameters indicating reproducibility – the coefficient of variation (COV) and the intraclass correlation coefficient (ICC) – were analyzed three times on the same day that mean blur rate (MBR) was measured using LSFG-NAVI. The sites analyzed were the retinal artery and vein, the optic disk, and the choroid. Following classification according to the Glaucoma Hemifield Test (GHT; SITA-Standard 30-2 program), the COV and ICC were examined in patients with (GHT+; 38 eyes, M:F = 20:18, average age 48.9 ± 12.8 years) and without (GHT-; 27 eyes, M:F = 13:14, average age 50.1 ± 8.7 years) abnormal glaucomatous visual fields.Results: For all subjects, the intrasession reproducibility of MBR in the optic disk (COV: 3.4 ± 2.0; ICC: 0.95) and choroid (COV: 4.7 ± 3.4; ICC: 0.98) was excellent. The reproducibility for the retinal vein (COV: 8.4 ± 5.6, ICC: 0.90) and retinal artery (COV: 10.9 ± 9.9, ICC: 0.9) was moderate. MBRs in the optic disk had good reproducibility in both the GHT+ group (COV: 3.8 ± 2.0; ICC: 0.97) and the GHT− group (COV: 2.9 ± 2.1; ICC: 0.95). Local assessment of the optic disk in normal or glaucoma patients showed that the COVs of the quadrant optic disk areas were best in the temporal area of MBR (3.4%, 4.2%, respectively).Conclusion: LSFG-NAVI showed favorable reproducibility in evaluation of retinal circulation of glaucoma patients, particularly in the optic disk and choroid.Keywords: ocular circulation, reproducibility, optic nerve, retina

Kazuko Omodaka, Toru Nakazawa, Yu Yokoyama, Hiroshi Doi, Nobuo Fuse, Kohji NishidaDepartment of Ophthalmology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Miyagi, JapanPurpose: To determine whether the best-corrected visual acuity (BCVA) is significantly correlated with the retinal nerve fiber layer thickness (RNFLT) in the different peripapillary areas in eyes with open-angle glaucoma (OAG).Patients and methods: Two hundred twenty-nine eyes of 159 patients with OAG were studied. The overall RNFLT and the RNFLT in the superior (S), temporal (T), inferior (I), and nasal (N) quadrants were measured by Stratus optical coherence tomography (OCT). In addition, the temporal RNFLT was measured for three 30° sectors with the mid-temporal (mT) sector at the three or nine o’clock position. The Spearman coefficient of correlation was calculated to determine whether a significant correlation existed between the RNFLT and the BCVA. Eyes with a BCVA < 20/20 were classified as having decreased BCVA. Results: There were significant correlations between the BCVA and the overall RNFLT, andalso between the BCVA and the RNFLT in the T, I, and S quadrants. The coefficient correlation between the BCVA and RNFLT was the highest in the mT sector (r = −0.40, P < 0.0001). Forty-eight eyes (21.1%) were classified as having decreased BCVA. The cut-off value of the mT sector for eyes with decreased VA was 39.0 μm.Conclusion: The highest correlation between the BCVA and the RNFLT in the mT sector was most likely due to the location of the maculopapillary bundle in this region of the optic disc. Our findings indicate that when the RNFLT in the mT sector is reduced to 40 μm, glaucoma treatment should be reconsidered.Keywords: retinal nerve fiber layer, low vision, peripapillary macular bundle

Ai Shimizu, Kazuichi Maruyama, Yu Yokoyama, Satoru Tsuda, Morin Ryu, Toru Nakazawa Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan Purpose: To investigate the characteristics of uveitic glaucoma (UG) and evaluate surgical treatments.Methods: This study examined a retrospective, nonrandomized comparative interventional case series of 105 UG patients (141 eyes) followed between April 1, 2001 and July 30, 2014 at the outpatient clinic of Tohoku University Hospital. The study group included 47 patients (47 eyes) who underwent glaucoma surgery: trabeculectomy, trabeculotomy, and trabectome surgery. The analysis used Kaplan–Meier life tables, with surgical failure defined as intraocular pressure ≧21mmHg or the need for additional glaucoma surgery.Results: UG patients represented 9.73% of our database of glaucoma patients. The mean follow-up period was 40.32±32.53 months. Seventy-one patients had granulomatous uveitis (67.62%) and 34 had nongranulomatous uveitis (32.38%). The causes of uveitis included sarcoidosis (n=25), Behçet’s disease (n=11), Vogt–Koyanagi–Harada disease (n=9), Posner–Schlossman syndrome (n=12), herpes simplex virus infectious uveitis (n=7), acute anterior uveitis (n=5), intermediate uveitis (n=4), scleritis (n=4), inflammatory bowel disease (n=4), varicella zoster virus uveitis (n=2), and others (n=6). An additional 16 patients were diagnosed with idiopathic UG. Surgical success rates were 82.86% for trabeculectomy, 62.50% for trabeculotomy, and 75.00% for trabectome. Significant risk factors for surgical failure included male sex (P=0.02), age less than 45 years (P=0.0009), nongranulomatous uveitis (P=0.04), and postoperative inflammation (P=0.01).Conclusion: Young male patients with nongranulomatous uveitis had a significant risk of surgical failure. Moreover, prolonged postoperative inflammation created a susceptibility to surgical failure, indicating the importance of postoperative inflammation reduction. Keywords: uveitic glaucoma, sarcoidosis, Behçet’s disease

Naoki Chiba, Kazuko Omodaka, Yu Yokoyama, Naoko Aizawa, Satoru Tsuda, Masayuki Yasuda, Takaaki Otomo, Shunji Yokokura, Nobuo Fuse, Toru Nakazawa Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan Background: The purpose of this study was to investigate the correlations between microcirculation in the optic disc, average peripapillary retinal nerve fiber layer thickness cupping parameters, and visual field defects in glaucoma patients with the generalized enlargement disc type. Methods: A total of 38 eyes from 38 glaucoma patients with the generalized enlargement disc type were included. The microcirculation of the optic nerve head was examined with laser speckle flow graphy, and the mean blur rate in all areas, in vessel area, and in tissue area were calculated using the laser speckle flow graphy analyzer software. Average peripapillary retinal nerve fiber layer thickness was measured using Stratus optical coherence tomography, and cupping parameters were accessed using the Heidelberg retina tomograph. The mean deviation in the Humphrey field analyzer (30-2 SITA standard) was analyzed. The correlation between these parameters was evaluated using the Spearman rank correlation coefficient. Results: The correlation coefficient of mean blur rate in all optic disc area to the average peripapillary retinal nerve fiber layer thickness, vertical C/D, and mean deviation were r = 0.7546 (P < 0.0001), r = –0.6208 (P < 0.0001), and r = 0.6010 (P = 0.0001), respectively. The mean blur rate in tissue area of the optic disc showed r = 0.7305 (P < 0.0001), r = –0.6438 (P < 0.0001), and r = 0.6338 (P < 0.0001). Conclusion: We found that the mean blur rate in the optic disc was significantly correlated with the average peripapillary retinal nerve fiber layer thickness, vertical C/D, and mean deviation in patients with the generalized enlargement disc type of glaucoma. In particular, the mean blur rate in tissue area was more highly correlated than the vessel area with other results of examination in glaucoma patients with the generalized enlargement disc type. Keywords: ocular blood flow, optic disc type, laser speckle flowgraphy, function, structure

Background The characteristics of glaucoma patients and their response to therapy may differ by institution, region and country. Therefore, clinicians should understand the distinctiveness of their patients. Here, we profile primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients at a major university hospital in Japan. Methods This study included 523 eyes from 523 POAG and NTG patients who underwent full clinical ophthalmologic evaluations at Tohoku University Hospital. Clinical characteristics such as age, sex, visual acuity, intraocular pressure, Humphrey field analyzer-measured mean deviation (MD) and MD slope were collected retrospectively. MD slope was calculated from MD data that included the first baseline measurement of MD and 4 subsequent, consecutive, reliable measurements of MD. Refractive error was analyzed in a subgroup with no history of refractive surgery, including intraocular lens implantation. Patient characteristics were analyzed separately in the groups of patients with low (