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Trabeculectomy using the Tenon advancement technique with a fornix-based conjunctival flap showed avascular bleb formation less frequently and had a significantly lower risk of developing bleb-related infections than trabeculectomy with a limbus-based conjunctival flap.To determine whether the Tenon advancement technique for trabeculectomy with a fornix-based (FB) conjunctival flap is effective in preventing bleb-related infections.This was a single-center, non-randomized retrospective cohort study of 998 eyes from 854 patients with glaucoma who underwent trabeculectomy with mitomycin C. Trabeculectomy procedures were categorized into three groups: limbus-based (LB, 296 eyes), FB without Tenon advancement (FBTA-, 167 eyes), and FB with Tenon advancement (FBTA+, 535 eyes). The cumulative incidence of bleb-related infections and the rate of surgical success during the 5-year postoperative follow-up period were analyzed using Kaplan-Meier survival analysis and Cox proportional hazards models. Intraocular pressure (IOP) reduction of20% from baseline or additional glaucoma surgeries were deemed a surgical failure. Surgical success with or without IOP-lowering medications was evaluated according to different IOP criteria.Ten eyes developed bleb-related infections (8 eyes in the LB group and 1 eye in both the FBTA- and FBTA+ groups each). The cumulative probability of bleb-related infections in the LB, FBTA-, and FBTA+ groups was 4.8±1.7% (± standard error), 0.8±0.8%, and 0.3±0.3%, respectively. The FBTA+ group had a significantly lower risk of bleb-related infections than the LB group (hazard ratio, 0.06; 95% confidence interval, 0.01 to 0.39; P=0.009). The FBTA+ group did not have a higher risk of surgical failure.The Tenon advancement technique for trabeculectomy using an FB conjunctival flap may be effective in preventing bleb-related infections without compromising surgical success.

Corneal hysteresis in both patients with untreated open angle glaucoma and normal individuals demonstrated significant diurnal variation independent of confounding factors and was higher in the nighttime than in the daytime.To investigate diurnal variations in corneal hysteresis (CH) in patients with untreated primary open angle glaucoma (POAG) and normal individuals by using an ocular response analyzer.This prospective study included 72 eyes of 53 patients with untreated POAG and 53 eyes of 47 normal individuals. Intraocular pressure (IOP) and CH were measured using Goldmann applanation tonometry (GAT) and ocular response analyzer, respectively, every 3 hours from 9:00 to 24:00. Mixed-effects models were used to determine factors associated with CH values and CH amplitude (maximum values minus minimum values) and to examine the diurnal variations in GAT IOP and CH in each group. Significant differences between time points were defined as significant variations.The diurnal average GAT IOP and CH in patients with POAG were significantly higher and lower than those in normal individuals ( P =0.001, 0.002). In the multivariate analysis, the larger central corneal thickness was associated with larger CH values in POAG and normal eyes (both P0.001). A larger amplitude of GAT IOP was significantly associated with a larger CH amplitude in POAG and normal eyes ( P =0.010, 0.013). CH, in both groups, showed similar significant diurnal variation and was higher in the nighttime than in the daytime, even after adjusting for confounding factors, while IOP showed an antiphase pattern.CH in both untreated POAG patients and normal participants demonstrated similar diurnal variations, that is, higher at night, independent of confounding factors. These findings suggest that viscoelastic properties of the cornea may fluctuate diurnally independent of IOP.

Recurrent painful ophthalmoplegic neuropathy (RPON) is a rare disorder, which typically occurs in children, and causes headaches and unilateral oculomotor palsy. Early high-dose corticosteroid therapy is recommended to rapidly resolve acute episodes. However, the pathophysiology and therapeutic options for this disorder remain to be fully elucidated. We report a case with typical clinical features of RPON successfully treated with beta-blocker eye drop instillation after the effects of high-dose corticosteroid and other therapies were not sufficient. We propose that beta-blocker eye drop instillation should be considered for patients with corticosteroid-resistant RPON.

Purpose To elucidate the relationship between changes in the choroidal structure and blood flow of the macula after trabeculectomy. Methods A prospective study of 30 eyes of 30 patients with glaucoma who underwent trabeculectomy. Enhanced depth imaging optical coherence tomography with choroidal image binarization and laser speckle flowgraphy of the macula were performed at baseline and 1, 3, and 6 months postoperatively. Mixed-effects models with adjustment for confounders were used to analyze longitudinal changes in the mean choroidal thickness (mCT), mean choroidal vascular thickness (mCVT), mean choroidal interstitial thickness (mCIT), and mean blur rate (MBR). Results The decrease in the intraocular pressure (IOP; 45%–51%) and axial length (0.5%–0.8%) and the increase in ocular perfusion pressure (OPP; 34%–38%), mCT (16%–19%), mCVT (16%–20%), mCIT (17%–20%), and MBR (22%–25%) were significant at each postoperative time point (all P < 0.001). In the multivariate analysis, the mCVT changes were positively correlated with the OPP and MBR changes (P = 0.04 and P < 0.001, respectively), whereas the mCIT changes were negatively correlated with IOP changes (P = 0.005). The MBR changes correlated significantly with changes in mCVT but not mCIT (P < 0.001 and P = 0.39, respectively). Conclusions Thickness changes in the intraluminal and extraluminal parts of the choroid were closely associated with changes in blood flow and IOP, respectively, although both parts thickened comparably after IOP reduction by trabeculectomy. Translational Relevance The choroid reacts to IOP reduction differently between the intraluminal and extraluminal areas, blood flow dependence in the vascular area, and IOP dependence in the stromal area.

To investigate the association between asymmetry of visual field (VF) defects and optic nerve head (ONH) blood flow in patients with glaucoma using laser speckle flowgraphy.In total, 170 eyes of 85 patients with primary open-angle glaucoma were included. Intraocular pressure, VF (Humphrey 24-2, SITA program), mean blur rate in the tissue area (MBR-T) of the ONH measured by laser speckle flowgraphy, axial length, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), disc area, cup/disc area ratio, and parapapillary atrophy (PPA) area was measured in each eye. The paired eyes were divided into better and worse eyes according to the mean deviation (MD) of VF, and intereye differences of various parameters (better MD eye minus worse MD eye) were examined. Factors associated with MD difference, MBR-T difference, or cpRNFLT difference were investigated.MD of the VF in better and worse eyes were -10.2±7.3 dB and -16.8±7.4 dB, respectively. In stepwise multiple regression analysis, MBR-T differences, cpRNFLT differences and sex (male) were significantly correlated with MD differences (β, 0.26, 0.21, 0.20; P=0.01, 0.04, 0.047, respectively). MD differences were significantly associated with MBR-T differences (β, 0.28; P=0.01). For cpRNFLT differences, differences in β-PPA area and MD differences were identified as significant factors (β, -0.26, 0.22; P=0.02, 0.04, respectively).Asymmetry of ONH blood flow is significantly associated with asymmetry of visual field defects in patients with glaucoma independently of cpRNFLT.

To investigate the spatial and temporal relationship between disc hemorrhage (DH) and structural progression in patients with primary open-angle glaucoma (POAG) in a 3-year prospective study.Prospective cohort study.Patients with POAG and intraocular pressure of ≤18 mmHg on monotherapy with prostaglandin analogs.Fundus photographs were taken at baseline and every 3 months for 3 years. Disc hemorrhage and structural progression were detected independently by flicker chronoscopy. If present, clock-hour disc locations in the right eye format and colocalization were determined. Statistical comparisons were based on mixed-effects models accounting for the correlation between different disc sites within the same eye and between fellow eyes in the same patient.Relationship between DH and structural progression at the same site.Among 195 eyes of 115 patients, DH appeared in 85 sites in 65 eyes (33.3%) and was most frequently at the 7 o'clock disc location (29.4%, P0.0001). Structural progression occurred at 63 sites of 52 eyes (26.7%) comparably in both superior and inferior hemidiscs, which was mostly detected as widening of the retinal nerve fiber layer defects (RNFLDs). Temporal RNFLD widening was common, whereas nasal widening occurred exclusively in the vertical quadrants (P = 0.035). Of 41 progression sites in eyes with DH, 28 sites (68.2%) had both DH and progression. Progression sites with DH were less common in the superior quadrant than in the inferior and temporal quadrants (P = 0.011). Eyes with DH had a significantly higher risk of progression than eyes without DH (hazard ratio, 3.72; P0.0001). For 63 progression sites, DH recurrence and more visits with DH at the progression site were significantly associated with shorter time to progression from baseline (P = 0.021, P = 0.017, respectively), whereas colocalization of DH and progression were not.In a 3-year prospective study with a Japanese POAG cohort, the relationship between DH and RNFLD and the pattern of RNFLD progression differed by disc location. The association between more frequent DH at the progression site and shorter time to progression indicates that DH may reflect vulnerability to same-site structural deterioration.

BACKGROUND/OBJECTIVES: To identify risk factors for glaucoma-related central visual field (VF) deterioration after vitrectomy with internal limiting membrane (ILM) peeling for epiretinal membrane (ERM). SUBJECTS/METHODS: A prospective cohort study consisting of cases with or without glaucoma (33 eyes of 33 patients in each group) who underwent vitrectomy with ILM peeling for ERM. Humphrey 10–2 VFs and ganglion cell complex (GCC) thickness were measured at baseline and about 3, 6, and 12 months postoperatively. Longitudinal changes in VF indices and factors associated with their postoperative changes were investigated using mixed-effects models, as was sectorwise total deviation (TD) analysis using six sectors consisting of outer/inner arcuate and cecocentral sectors in each hemifield. RESULTS: VF mean deviation significantly deteriorated postoperatively only in the glaucoma group (P

ObjectiveThe relationship between retinal structure and function of glaucomatous eyes has attracted a great deal of research attention. However, visual field tests are conducted under monocular condition, and ophthalmic imaging was performed in patients without occlusion. We aimed to assess the objective ocular cyclodeviation between monocular occlusion and binocular conditions using fundus photography.Methods and analysisThis study included 76 healthy participants. We obtained six photos of the right eye of each patient using fundus photography. Three of the photographs were taken under monocular conditions, and the other three, under binocular conditions. We measured the optic disc margin-fovea angle (MFA) of the line connecting one point of the disc limbus and the fovea. One-way repeated analysis of variance was used to compare the angles under both conditions. We also examined the direction of ocular rotation under the binocular condition regarding the monocular condition.ResultsThe MFAs were 12.12°±3.83° and 12.19°±3.95° under the monocular and binocular conditions, respectively. There was no significant difference in both MFAs (F=1.19, p=0.28). The mean cyclodeviation was 0.07°±0.80° (range: −2.40° to +2.75°). A total of 38 eyes showed excycloduction, while another 38 showed incycloduction.ConclusionSignificant cyclodeviation did not occur regardless of the existence of an occlusion. When examining the relationship between retinal structure and function, the difference in rotation angle under both conditions need not be taken into consideration if the other disease did not cause pathological cyclodeviation.

Background/aims To assess the role of specific visual subfields in collisions with oncoming cars during simulated driving in patients with advanced glaucoma. Methods Normal subjects and patients with glaucoma with mean deviation

Purpose We assessed the ability to detect preperimetric glaucoma (PPG) based on asymmetry in the thickness of the macular inner retinal layers measured by spectral-domain optical coherence tomography. Methods We studied 45 normal eyes and 50 PPG eyes retrospectively. Three-dimensional optical coherence tomography macular area scans were used to obtain the thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer/inner plexiform layer (GCL/IPL), and ganglion cell complex (GCC). We calculated the thickness differences between the upper and lower macular hemispheres for the corresponding superpixels, then evaluated the mean absolute value of the thickness differences and the number of superpixels in which the thickness difference was greater than X µm, where X is an integer number from 1 to 10. Areas under the receiver operating characteristic curves (AUCs) for their PPG diagnostic performances were compared to the average thickness measurements of the total and hemiretinal sectors. X was determined at the maximum AUC value. Results The AUC for the mean absolute value of the difference in GCL/IPL thickness (0.923) was higher than the difference in RNFL and GCC thickness (0.710 and 0.905, respectively). The AUC for the number of superpixels in which the GCL/IPL thickness difference was greater than 8 µm (X = 8) was 0.914. The ability to diagnose PPG using these GCL/IPL parameters was statistically higher than for total or superior and inferior hemiretinal GCL/IPL thicknesses. Conclusions Asymmetry in the thickness of the GCL/IPL shows good PPG diagnostic performance. Translational relevance This approach would be useful in the early detection of glaucoma.

Daisuke Takemoto, Tomomi Higashide, Yoshiaki Saito, Shinji Ohkubo, Sachiko Udagawa, Hisashi Takeda, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Purpose: We conducted a prospective study in patients with normal-tension glaucoma (NTG) who received either isopropyl unoprostone or latanoprost. We compared the drugs in terms of their effects on intraocular pressure (IOP) and visual field loss progression over a 3-year period. Study design: Prospective, randomized controlled study. Methods: We enrolled 48 patients with newly diagnosed NTG at Kanazawa University Hospital. Eligible patients were randomly allocated (1:1) to receive either unoprostone or latanoprost ophthalmic solutions. The primary outcomes were IOP changes and visual field deterioration within 36 months. Visual field changes were analyzed: the cumulative survival rates were calculated in terms of mean deviation, pattern standard deviation, and total deviation of the upper or lower hemi-visual field, each visual field sector, and guided progression analysis. In addition, we evaluated the progression of glaucomatous optic disc changes using fundus photography and confocal scanning laser ophthalmoscopy. Results: The mean pretreatment IOP was 15.0±2.4 mmHg in the Unoprostone group and 15.2±1.9 mmHg in the Latanoprost group. The mean IOP during the treatment period was 13.7±2.3 mmHg in the Unoprostone group and 13.0±1.8 mmHg in the Latanoprost group. In both groups, the IOP decreased significantly (p

PURPOSE To investigate postoperative changes and prognostic factors of visual impairment after vitrectomy for unilateral epiretinal membrane. METHODS A prospective observational study on 45 eyes from 45 patients with unilateral idiopathic epiretinal membrane who underwent vitrectomy. Visual parameters (best-corrected visual acuity, metamorphopsia using M-CHARTS, and aniseikonia using the New Aniseikonia Test) and spectral domain optical coherence tomography parameters (macular retinal layer thickness and microstructure of the outer retina) were measured preoperatively and 6 and 12 months postoperatively. Statistical analyses included linear mixed-effects models for the longitudinal changes and prognostic factors of visual parameters. RESULTS Best-corrected visual acuity and horizontal metamorphopsia improved significantly from 6 months after surgery (P < 0.001), whereas aniseikonia decreased significantly only at 12 months (P = 0.015). Vertical metamorphopsia remained unchanged. Preoperative inner nuclear layer thickness was significantly correlated with preoperative metamorphopsia. Besides baseline values, best-corrected visual acuity had no significant prognostic factors, but preoperative ellipsoid zone disruption had a negative direction of association with postoperative metamorphopsia (coefficients: -0.37 and -0.62, P = 0.015 and 0.006 for horizontal and vertical metamorphopsia, respectively), and preoperative horizontal metamorphopsia had a positive direction of association with postoperative aniseikonia (coefficient: 1.77, P = 0.002). CONCLUSION After vitrectomy, postoperative changes and prognostic factors for unilateral epiretinal membrane differed for best-corrected visual acuity, metamorphopsia, and aniseikonia.

Purpose To investigate the effect of trabeculectomy on the waveform changes of laser speckle flowgraphy (LSFG) in the optic nerve head (ONH) in patients with glaucoma. Methods Forty-eight eyes of 48 patients with open angle glaucoma were included in this prospective study. LSFG was performed before and 1, 3, and 6 months after trabeculectomy. Longitudinal changes in average mean blur rate (MBR), blow out score (BOS), resistivity index (RI), falling rate, skew, acceleration time index, and blow out time in the tissue area of the ONH were analyzed by using mixed-effects models. Results Intraocular pressure (IOP) decreased and ocular perfusion pressure increased significantly at each postoperative time point (P < 0.001, each). BOS increased (P < 0.001, each) and RI decreased (P < 0.001, each) significantly at each postoperative time point, although average MBR and other waveform parameters did not change significantly. Multivariate analyses revealed that younger age (coefficients = -0.13 and 0.0014, P = 0.006 and 0.03 for BOS change and RI change, respectively), worse baseline mean deviation of visual fields (coefficients = -0.18 and 0.0026, P = 0.009 and 0.005), larger IOP reduction (coefficients = -0.29 and 0.0037, P < 0.001, each), and larger pulse rate increase (coefficients = 0.17 and -0.0024, P < 0.001, each) are significantly associated with postoperative BOS increase and RI decrease. Conclusions Given that postoperative BOS increased and RI decreased with the average MBR remaining unchanged, IOP reduction by trabeculectomy may contribute to stable blood flow throughout the duration of the heartbeat in the tissue area of the ONH.

金沢大学附属病院眼科, Purpose: Traffic accidents are associated with the visual function of drivers, as well as many other factors. Driving simulator systems have the advantage of controlling for traffic- and automobile-related conditions, and using pinhole glasses can control the degree of concentric concentration of the visual field. We evaluated the effect of concentric constriction of the visual field on automobile driving, using driving simulator tests. Methods: Subjects meeting criteria for normal eyesight were included in the study. Pinhole glasses with variable aperture sizes were adjusted to mimic the conditions of concentric visual field constrictions of 10° and 15°, using a CLOCK CHART®. The test contained 8 scenarios (2 oncoming right-turning cars and 6 jump-out events from the side). Results: Eighty-eight subjects were included in the study; 37(mean age = 52.9±15.8 years) subjects were assigned to the 15° group, and 51 (mean = 48.6±15.5 years) were assigned to the 10° group. For all 8 scenarios, the number of accidents was significantly higher among pinhole wearing subjects. The average number of all types of accidents per person was significantly higher in the pinhole 10° group (4.59±1.81) than the pinhole 15° group (3.68±1.49) (P = 0.032). The number of accidents associated with jump-out scenarios, in which a vehicle approaches from the side on a straight road with a good view, was significantly higher in the pinhole 10° group than in the pinhole 15° group. Conclusions: Concentric constriction of the visual field was associated with increased number of traffic accidents. The simulation findings indicated that a visual field of 10° to 15° may be important for avoiding collisions in places where there is a straight road with a good view. © 2018 Udagawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Purpose To compare the sectoral structure-function relationships in glaucoma between two structural parameters, vessel density (VD) and thickness, in the peripapillary retinal nerve fiber layer (RNFL). Methods Optical coherence tomography (OCT) angiography (AngioVue/RTVue-XR) for VD and OCT (RS-3000) for peripapillary RNFL thickness were performed in 129 eyes from 129 subjects (94 glaucoma, 17 glaucoma suspects, and 18 normal eyes). Humphrey visual field (VF) tests were performed using a SITA standard 24-2 program. Sectoral structure-function relationships based on the Garway-Heath map were compared between VD and thickness using a semipartial correlation coefficient (sr) and partial residual plots determined by multiple linear regression models controlling for the effects of sex, age, axial length, disc area, beta- and gamma- parapapillary atrophy (PPA) zones, and signal strength index (SSI). Results For all VF sectors, the sr2 of VD was largest when the VD sector corresponded to the VF sector (sr2: 0.17-0.39). In contrast, in only three sectors was the sr2 of thickness largest when the thickness sector corresponded to the VF sector (sr2: 0.02-0.34): the inferior temporal, temporal, and superior temporal sectors. The partial residual plots against VD showed more linear relationships with VF sensitivity than those against thickness in the qualitative evaluation of fitting by locally weighted scatterplot smoothing. Eyes with larger SSI had higher VD, whereas eyes with a larger extension of the PPA zone into the VD measurement area had lower VD. Conclusions Peripapillary RNFL VD and thickness have different characteristic sectoral structure-function relationships in glaucoma.

DNA topoisomerase inhibitors are effective chemotherapeutic agents on several solid tumor cells. They induce a specific signaling cascade that executes an active cell death process (apoptosis), including caspase activation, and the blockage of the signaling is associated with drug-resistance of tumor cells. However, little is known about the initial signal transduction induced by the agents. In the present study, we screened genes that are initially upregulated in caspase-independent manner. We found that the activating transcription factor 3 (ATF3) protein, a repressor of cyclic-AMP responsive element (CRE)-dependent transcription, was strongly induced among CRE-BP/ATF members and subsequently accumulated in nuclei following camptothecin or etoposide treatment. During induction of apoptosis, the accumulation and the nuclear translocation of ATF3 coincided with the activation of caspase protease and were not inhibited by the broad caspase inhibitor Z-VAD-fmk, indicating that ATF3 induction is not a downstream event of caspase activation. When stably or transiently overexpressed, ATF3 markedly accelerated the drug-induced apoptosis and enhanced caspase protease activation. ATF3 strongly downregulated CRE-dependent transcription, while ATF3 did not affect the expression levels of Bcl-2, Bcl-x, or Bax. Our present results indicate that ATF3 plays a critical role in accelerating caspase protease activation and apoptosis. Since CRE-dependent transcription functions as cell survival signaling, ATF3 could control the upstream signaling of apoptosis by repressing CRE-dependent gene expression of cell survival factors. © 2001 Wiley-Liss, Inc.