Additive effects of brimonidine tartrate 0.1%/brinzolamide 1% fixed-dose combination in prostaglandin analog-treated Japanese glaucoma patients.

PURPOSE: A brimonidine tartrate 0.1%/brinzolamide 1% fixed-dose combination (BBFC) was recently approved for glaucoma and ocular hypertension treatment in Japan. We investigated the efficacy and safety of BBFC used concomitantly with prostaglandin analogs (PG) or a PG/beta-blocker fixed-dose combination (PG/beta FC). STUDY DESIGN: This was a prospective, open-label, multicenter study. PATIENTS AND METHODS: We enrolled Japanese patients with open-angle glaucoma. BBFC (Ailamide) was concomitantly administered to either the PG or the PG/beta FC group, and intraocular pressure (IOP) and safety were evaluated at 4 and 12 weeks. The groups were stratified into low and high IOP baseline groups based on the median baseline IOP. RESULTS: We enrolled 100 patients, 91 of whom completed the 12-week follow-up. The mean ages were 67.1 and 65.7 years in the PG group (n = 45, baseline IOP of 15.7 ± 2.3 mmHg) and the PG/beta FC group (n = 46, baseline IOP of 16.3 ± 2.3 mmHg), respectively. After BBFC administration, IOPs at 4 and 12 weeks were 13.0 ± 2.0 and 13.0 ± 2.6 mmHg (P < 0.0001) in the PG group, respectively, and 13.7 ± 2.4 and 13.7 ± 2.2 mmHg (P < 0.0001) in the PG/beta FC group, respectively. IOP decreased by - 2.0 ± 1.8 mmHg (P < 0.0001) and -1.9 ± 1.4 mmHg (P < 0.0001) in the low baseline PG group (14.1 mmHg) and low baseline PG/beta FC group (14.8 mmHg) at 12 weeks, respectively. Sixteen adverse events were identified, all of which were common and did not affect visual acuity. CONCLUSIONS: BBFC can be used concomitantly with PG or PG/beta FC to reduce IOP without serious complications.

Bacterial Community Composition Under Paddy Conditions Is More Strongly Affected by the Difference in Soil Type than by Field Management.

In this study, we aimed to investigate the effects of soil type and field management on bacterial communities in paddy soils, taking into account the differences in soil physicochemical properties. We collected soil samples from 51 paddy fields in six prefectures in Japan. The paddy fields were managed under organic regimes (26 fields), natural-farming regimes (12 fields), or conventional regimes (13 fields). The paddy fields were classified into four soil types: andosol, gray lowland soil, gley soil, and gray upland soil. Soil DNA was extracted from the soil samples collected 2 to 10 weeks after the flooding, and the 16S rRNA gene amplicon sequencing analysis was performed. The bacterial community compositions were dominated by the phylum Proteobacteria, Chloroflexi, Actinobacteria, Acidobacteria, and Firmicutes in all fields. The difference in soil type had significant effects on α-diversities of the bacterial communities, although the field management had no effect. The soil bacterial communities in the gley soils and gray upland soils individually formed different groups from those in the other soils, while the andosol and gray lowland soils tended to form relatively similar bacterial communities. On the other hand, the effects of the field management were estimated to be smaller than those of soil type. The ß-diversity of the bacterial community compositions were significantly correlated with soil pH, total nitrogen content, total carbon content, and divalent iron content. Our results suggest that the soil microbial community in paddy fields may be strongly influenced by soil physiochemical properties derived from differences in soil type.

Trabeculectomy Tenon Advancement Technique May Reduce Bleb-Related Infections.

PRCIS: Trabeculectomy using the Tenon advancement technique with a fornix-based (FB) 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. PURPOSE: To determine whether the Tenon advancement technique for trabeculectomy with a FB conjunctival flap is effective in preventing bleb-related infections. MATERIALS AND METHODS: This was a single-center, nonrandomized retrospective cohort study of 998 eyes from 854 patients with glaucoma who underwent trabeculectomy with mitomycin C. Trabeculectomy procedures were categorized into 3 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 of <20% from baseline or additional glaucoma surgeries was deemed a surgical failure. Surgical success with or without IOP-lowering medications was evaluated according to different IOP criteria. RESULTS: 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. CONCLUSION: The Tenon advancement technique for trabeculectomy using an FB conjunctival flap may be effective in preventing bleb-related infections without compromising surgical success.

Relationship Between Changes in the Choroidal Structure and Blood Flow of the Macula After Trabeculectomy.

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.

A Case of Recurrent Painful Ophthalmoplegic Neuropathy Successfully Treated with Beta-blocker Eye Drop Instillation.

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.

The association of primary aldosteronism with glaucoma-related fundus abnormalities.

PURPOSE: To elucidate glaucoma-related fundus abnormalities in patients with primary aldosteronism (PA). METHODS: The study compared 272 eyes from 137 PA patients and 352 eyes from 177 control subjects selected randomly from 1173 participants of a public glaucoma screening. The presence of glaucomatous optic disc appearance (rim thinning and cup enlargement) and retinal nerve fiber layer defects (RNFLDs) was determined independently from fundus photographs. The results were compared between the PA and control groups. RESULTS: There were 9 patients (6.6%) with glaucomatous optic disc abnormalities in the PA group and 10 cases (5.6%) identified in the control group (p = 0.92). RNFLDs were detected more frequently in the PA group (55 eyes, 20.2%) than in the control group (26 eyes, 7.4%; p<0.001). The two types of RNFLDs were classified as either having their central ends at the disc margin (D) or away from the disc margin and around the retinal vessels (V). Type D and V RNFLDs were detected in 35 (12.9%) and 26 (9.6%) eyes in the PA group and in 25 (7.1%) and 4 (1.1%) eyes in the control group, respectively. Both types of RNFLDs were more frequent in the PA group than in the control group (Type D and V, p = 0.03, <0.001, respectively). CONCLUSION: Although the prevalence of glaucomatous optic disc appearance did not differ between the two groups, RNFLDs were more frequent in PA patients than in the control group. Moreover, RNFLDs with their central ends located around retinal vessels were characteristic of PA patients.

Spatial and Temporal Relationship between Structural Progression and Disc Hemorrhage in Glaucoma in a 3-Year Prospective Study.

PURPOSE: 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. DESIGN: Prospective cohort study. PARTICIPANTS: Patients with POAG and intraocular pressure of ≤18 mmHg on monotherapy with prostaglandin analogs. METHODS: 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. MAIN OUTCOME MEASURES: Relationship between DH and structural progression at the same site. RESULTS: 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%, P < 0.0001). 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; P < 0.0001). 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. CONCLUSIONS: 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.

Ability of Macular Inner Retinal Layer Thickness Asymmetry Evaluated by Optical Coherence Tomography to Detect Preperimetric Glaucoma.

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.

Assessment of objective ocular cyclodeviation under monocular condition and binocular condition using fundus photography.

OBJECTIVE: The 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 ANALYSIS: This 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. RESULTS: The 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. CONCLUSION: Significant 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.

Effectiveness of trabeculectomy with mitomycin C for glaucomatous eyes with low intraocular pressure on treatment eye drops.

PURPOSE: To examine the efficacy and safety of current trabeculectomy with mitomycin C in Japan for glaucomatous eyes with low intraocular pressure (IOP). METHODS: Two hundred ninety-four eyes of 294 patients with IOP ≤21 mmHg before surgery were studied; all patients were participants in the Collaborative Bleb-related Infection Incidence and Treatment Study (CBIITS), a multicentre, prospective, cohort study conducted at 34 ophthalmological institutions throughout Japan. All eyes had an intraocular pressure ≤ 21 mmHg and had undergone trabeculectomy alone or phacotrabeculectomy. Two success criteria were used: Criterion A comprised 20% reduction of baseline IOP and Criterion B comprised 30% reduction of baseline IOP. The primary outcome was the success rate for each of these criteria. RESULTS: The qualified success rates were 87.3% for Criterion A and 42.0% for Criterion B at 5 years. Mean IOP was significantly reduced, from 16.7 ± 2.7 to 11.6 ± 4.0 mmHg at 5 years after trabeculectomy (p < 0.0001); the number of anti-glaucoma medications significantly decreased from 2.7 ± 1.1 to 1.0 ± 1.2 (p < 0.0001) at 5 years after the surgery. Three or more trabeculectomies, and needling were related to increased risk of failure. Incidences of postoperative hyphema, infection, shallow anterior chamber and bleb leakage were 2.4%, 2.4%, 2.0% and 3.4%, respectively. CONCLUSIONS: This study showed that trabeculectomy with mitomycin C is an effective procedure with few surgical complications for reducing IOP in patients, even if preoperative IOP was within the normal range.

Maize polyamine oxidase in the presence of spermine/spermidine induces the apoptosis of LoVo human colon adenocarcinoma cells.

Amine oxidases, which contribute to the regulation of polyamine levels, catalyze the oxidative deamination of polyamines to generate H2O2 and aldehyde(s). In this study, and at least to the best of our knowledge, maize polyamine oxidase (ZmPAO) was used for the first time with the aim of identifying a novel strategy for cancer therapy. The cytotoxicity and the mechanisms of cell death induced by the enzymatic oxidation products of polyamine generated by ZmPAO were investigated. Exogenous spermine and ZmPAO treatment decreased cell viability in a spermine dose­ and time­dependent manner, particularly, the viability of the multidrug­resistant (MDR) colon adenocarcinoma cells, LoVo DX, when compared with drug­sensitive ones (LoVo WT). Further analyses revealed that H2O2 derived from spermine was mainly responsible for the cytotoxicity. Flow cytometric analysis revealed that treatment with ZmPAO and spermine increased the apoptotic population of LoVo WT and LoVo DX cells. In addition, we found that treatment with ZmPAO and spermine markedly reduced mitochondrial membrane potential in the LoVo DX cells, in agreement with the results of cell viability and apoptosis assays. Transmission electron microscopic observations supported the involvement of mitochondrial depolarization in the apoptotic process. Therefore, the dysregulation of polyamine metabolism in tumor cells may be a potential therapeutic target. In addition, the development of MDR tumor cells is recognized as a major obstacle in cancer therapy. Therefore, the design of a novel therapeutic strategy based on the use of this combination may be taken into account, making this approach attractive mainly in treating MDR cancer patients.

Effects of Trabeculectomy on Waveform Changes of Laser Speckle Flowgraphy in Open Angle Glaucoma.

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.

The antioxidant, aged garlic extract, exerts cytotoxic effects on wild-type and multidrug-resistant human cancer cells by altering mitochondrial permeability.

Aged garlic extract (AGE) has been shown to possess therapeutic properties in cancer; however its mechanisms of action are unclear. In this study, we demonstrate by MTT assay that AGE exerts an anti-proliferative effect on a panel of both sensitive and multidrug-resistant (MDR) human cancer cell lines and enhances the effects of hyperthermia (42˚C) on M14 melanoma cells. The evaluation of the mitochondrial activity in whole cancer cells treated with AGE, performed by cytofluorimetric analysis in the presence of the lipophilic cationic fluorochrome JC-1, revealed the occurrence of dose-dependent mitochondrial membrane depolarization. Membrane potential was measured by the TPP+ selective electrode. In order to shed light on its mechanisms of action, the effects of AGE on isolated rat liver mitochondria were also examined. In this regard, AGE induced a mitochondrial membrane hyperpolarization of approximately 15 mV through a mechanism that was similar to that observed with the ionophores, nigericin or salinomycin, by activating an exchange between endogenous K+ with exogenous H+. The prolonged incubation of the mitochondria with AGE induced depolarization and matrix swelling, indicative of mitochondrial permeability transition induction that, however, occurs through a different mechanism from the well-known one. In particular, the transition pore opening induced by AGE was due to the rearrangement of the mitochondrial membranes following the increased activity of the K+/H+ exchanger. On the whole, the findings of this study indicate that AGE exerts cytotoxic effects on cancer cells by altering mitochondrial permeability. In particular, AGE in the mitochondria activates K+/H+ exchanger, causes oxidative stress and induces mitochondrial permeability transition (MPT).

The effect of concentric constriction of the visual field to 10 and 15 degrees on simulated motor vehicle accidents.

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.

Intraocular pressure and visual field changes in normal-tension glaucoma patients treated using either unoprostone or latanoprost: a prospective comparative study.

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<0.001) from baseline after treatment. The posttreatment IOP values were significantly lower in the Latanoprost group than in the Unoprostone group (p=0.023). Regarding the 3-year cumulative survival rate of visual field loss progression, there were no significant differences between groups in any parameters of the visual field or guided progression analysis. There were no significant differences between groups in disc changes. CONCLUSIONS: No significant differences were found between groups with regard to the visual field and structural progression in patients with NTG, although unoprostone was less effective than latanoprost in lowering the IOP.

Comparison of Sectoral Structure-Function Relationships in Glaucoma: Vessel Density Versus Thickness in the Peripapillary Retinal Nerve Fiber Layer.

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.

The role of specific visual subfields in collisions with oncoming cars during simulated driving in patients with advanced glaucoma.

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 <-12 dB in both eyes (Humphrey Field Analyzer 24-2 SITA-S program) used a driving simulator (DS; Honda Motor, Tokyo). Two scenarios in which oncoming cars turned right crossing the driver's path were chosen. We compared the binocular integrated visual field (IVF) in the patients who were involved in collisions and those who were not. We performed a multivariate logistic regression analysis; the dependent parameter was collision involvement, and the independent parameters were age, visual acuity and mean sensitivity of the IVF subfields. RESULTS: The study included 43 normal subjects and 100 patients with advanced glaucoma. And, 5 of the 100 patients with advanced glaucoma experienced simulator sickness during the main test and were thus excluded. In total, 95 patients with advanced glaucoma and 43 normal subjects completed the main test of DS. Advanced glaucoma patients had significantly more collisions than normal patients in one or both DS scenarios (p<0.001). The patients with advanced glaucoma who were involved in collisions were older (p=0.050) and had worse visual acuity in the better eye (p<0.001) and had lower mean IVF sensitivity in the inferior hemifield, both 0°-12° and 13°-24° in comparison with who were not involved in collisions (p=0.012 and p=0.034). A logistic regression analysis revealed that collision involvement was significantly associated with decreased inferior IVF mean sensitivity from 13° to 24° (p=0.041), in addition to older age and lower visual acuity (p=0.018 and p<0.001). CONCLUSIONS: Our data suggest that the inferior hemifield was associated with the incidence of motor vehicle collisions with oncoming cars in patients with advanced glaucoma.

Milestones and recent discoveries on cell death mediated by mitochondria and their interactions with biologically active amines.

Mitochondria represent cell "powerhouses," being involved in energy transduction from the electrochemical gradient to ATP synthesis. The morphology of their cell types may change, according to various metabolic processes or osmotic pressure. A new morphology of the inner membrane and mitochondrial cristae, significantly different from the previous one, has been proposed for the inner membrane and mitochondrial cristae, based on the technique of electron tomography. Mitochondrial Ca(2+) transport (the transporter has been isolated) generates reactive oxygen species and induces the mitochondrial permeability transition of both inner and outer mitochondrial membranes, leading to induction of necrosis and apoptosis. In the mitochondria of several cell types (liver, kidney, and heart), mitochondrial oxidative stress is an essential step in the induction of cell death, although not in brain, in which the phenomenon is caused by a different mechanism. Mitochondrial permeability transition drives both apoptosis and necrosis, whereas mitochondrial outer membrane permeability is characteristic of apoptosis. Adenine nucleotide translocase remains the most important component involved in membrane permeability, with the opening of the transition pore, although other proteins, such as ATP synthase or phosphate carriers, have been proposed. Intrinsic cell death is triggered by the release from mitochondria of proteic factors, such as cytochrome c, apoptosis inducing factor, and Smac/DIABLO, with the activation of caspases upon mitochondrial permeability transition or mitochondrial outer membrane permeability induction. Mitochondrial permeability transition induces the permeability of the inner membrane in sites in contact with the outer membrane; mitochondrial outer membrane permeability forms channels on the outer membrane by means of various stimuli involving Bcl-2 family proteins. The biologically active amines, spermine, and agmatine, have specific functions on mitochondria which distinguish them from other amines. Enzymatic oxidative deamination of spermine by amine oxidases in tumor cells may produce reactive oxygen species, leading to transition pore opening and apoptosis. This process could be exploited as a new therapeutic strategy to combat cancer.

Ser/Thr kinases and polyamines in the regulation of non-canonical functions of elongation factor 1A.

The link between eukaryotic translation elongation factor 1A (eEF1A) and signal transduction pathways through the regulatory mechanism of phosphorylation has never been considered. In this review, we focus on the different kinases that recognize the Ser and Thr residues of the eEF1A1 and eEF1A2 isoforms and regulate their involvement in different cellular processes like cell survival and apoptosis. In this context, polyamines seem to play a role in the regulation of the translation elongation process by modulating the Ser/Thr kinases involved in the phosphorylation of translation elongation factors.