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.

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.

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.

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.

Spermine cycling in mitochondria is mediated by adenine nucleotide translocase activity: mechanism and pathophysiological implications.

Spermine, besides to be transported in mitochondria by an energy dependent electrophoretic mechanism, can be also released by two different mechanisms. The first one is induced in deenergizing conditions by FCCP or antimycin A and it is mediated by an electroneutral exchange spermine protons. The second one takes place in energizing conditions during the activity of the adenine nucleotide translocase and is mediated by an electroneutral symport mechanism involving the efflux in co-transport of spermine and phosphate and the exchange of exogenous ADP with endogenous ATP. The triggering of this mechanism permits an alternating cycling of spermine across the mitochondrial membrane, that is spermine is transported or released by energized mitochondria in the absence or presence of ATP synthesis, respectively. The physiological implications of this cycling of spermine are related to the induction or prevention of mitochondrial permeability transition and, consequently, on apoptosis or its prevention.

Stability of spermine oxidase to thermal and chemical denaturation: comparison with bovine serum amine oxidase.

Spermine oxidase (SMOX) is a flavin-containing enzyme that specifically oxidizes spermine to produce spermidine, 3-aminopropanaldehyde and hydrogen peroxide. While no crystal structure is available for any mammalian SMOX, X-ray crystallography showed that the yeast Fms1 polyamine oxidase has a dimeric structure. Based on this scenario, we have investigated the quaternary structure of the SMOX protein by native gel electrophoresis, which revealed a composite gel band pattern, suggesting the formation of protein complexes. All high-order protein complexes are sensitive to reducing conditions, showing that disulfide bonds were responsible for protein complexes formation. The major gel band other than the SMOX monomer is the covalent SMOX homodimer, which was disassembled by increasing the reducing conditions, while being resistant to other denaturing conditions. Homodimeric and monomeric SMOXs are catalytically active, as revealed after gel staining for enzymatic activity. An engineered SMOX mutant deprived of all but two cysteine residues was prepared and characterized experimentally, resulting in a monomeric species. High-sensitivity differential scanning calorimetry of SMOX was compared with that of bovine serum amine oxidase, to analyse their thermal stability. Furthermore, enzymatic activity assays and fluorescence spectroscopy were used to gain insight into the unfolding process.

Intraocular Pressure Outcomes and Risk Factors for Failure in the Collaborative Bleb-Related Infection Incidence and Treatment Study.

PURPOSE: To evaluate the efficacy and safety of trabeculectomy for patients with glaucoma who were enrolled in the Collaborative Bleb-related Infection Incidence and Treatment Study (CBIITS). DESIGN: Multicenter, prospective, cohort study. PARTICIPANTS: A total of 829 eyes in 829 patients with glaucoma who had undergone trabeculectomy alone or trabeculectomy combined with phacoemulsification at 34 clinical centers were examined in this study. MAIN OUTCOME MEASURES: Intraocular pressures (IOPs, in millimeters of mercury), risk factors for surgical failure, and surgical complications. METHODS: The enrollment period was 2 years, and follow-up was conducted every 6 months for up to 5 years. Outcomes were measured at 6-month intervals. Four levels of success were defined by achievement of the following IOP: (A) 4

Pathophysiological implications of mitochondrial oxidative stress mediated by mitochondriotropic agents and polyamines: the role of tyrosine phosphorylation.

Mitochondria, once merely considered as the "powerhouse" of cells, as they generate more than 90 % of cellular ATP, are now known to play a central role in many metabolic processes, including oxidative stress and apoptosis. More than 40 known human diseases are the result of excessive production of reactive oxygen species (ROS), bioenergetic collapse and dysregulated apoptosis. Mitochondria are the main source of ROS in cells, due to the activity of the respiratory chain. In normal physiological conditions, ROS generation is limited by the anti-oxidant enzymatic systems in mitochondria. However, disregulation of the activity of these enzymes or interaction of respiratory complexes with mitochondriotropic agents may lead to a rise in ROS concentrations, resulting in oxidative stress, mitochondrial permeability transition (MPT) induction and triggering of the apoptotic pathway. ROS concentration is also increased by the activity of amine oxidases located inside and outside mitochondria, with oxidation of biogenic amines and polyamines. However, it should also be recalled that, depending on its concentration, the polyamine spermine can also protect against stress caused by ROS scavenging. In higher organisms, cell signaling pathways are the main regulators in energy production, since they act at the level of mitochondrial oxidative phosphorylation and participate in the induction of the MPT. Thus, respiratory complexes, ATP synthase and transition pore components are the targets of tyrosine kinases and phosphatases. Increased ROS may also regulate the tyrosine phosphorylation of target proteins by activating Src kinases or phosphatases, preventing or inducing a number of pathological states.

The 5-year incidence of bleb-related infection and its risk factors after filtering surgeries with adjunctive mitomycin C: collaborative bleb-related infection incidence and treatment study 2.

PURPOSE: To report the 5-year incidence of bleb-related infection after mitomycin C-augmented glaucoma filtering surgery and to investigate the risk factors for infections. DESIGN: Prospective, observational cohort study. PARTICIPANTS: A total of 1098 eyes of 1098 glaucoma patients who had undergone mitomycin C-augmented trabeculectomy or trabeculectomy combined with phacoemulsification and intraocular lens implantation performed at 34 clinical centers. METHODS: Patients were followed up at 6-month intervals for 5 years, with special attention given to bleb-related infections. The follow-up data were analyzed via Kaplan-Meier survival analysis and the Cox proportional hazards model. MAIN OUTCOME MEASURES: Incidence of bleb-related infection over 5 years and risk factors for infections. RESULTS: Of the 1098 eyes, a bleb-related infection developed in 21 eyes. Kaplan-Meier survival analysis revealed that the incidence of bleb-related infection was 2.2±0.5% (cumulative incidence ± standard error) at the 5-year follow-up for all cases, whereas it was 7.9±3.1% and 1.7±0.4% for cases with and without a history of bleb leakage, respectively (P = 0.000, log-rank test). When only eyes with a well-functioning bleb were counted, it was 3.9±1.0%. No differences were found between the trabeculectomy cases and the combined surgery cases (P = 0.398, log-rank test) or between cases with a fornix-based flap and those with a limbal-based flap (P = 0.651, log-rank test). The Cox model revealed that a history of bleb leakage and younger age were risk factors for infections. CONCLUSIONS: The 5-year cumulative incidence of bleb-related infection was 2.2±0.5% in eyes treated with mitomycin C-augmented trabeculectomy or trabeculectomy combined with phacoemulsification and intraocular lens implantation in our prospective, multicenter study. Bleb leakage and younger age were the main risk factors for infections.

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.

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.

Effective RNA interference in cultured silkworm cells mediated by overexpression of Caenorhabditis elegans SID-1.

RNA interference (RNAi) is a conserved mechanism that catalyzes sequence-specific gene silencing and has been used for loss-of-function genetic screens in many organisms. Here, we demonstrated that the expression of Caenorhabditis elegans SID-1 (CeSID-1) could trigger effective gene silencing in the cultured silkworm cell line, BmN4 (BmN4-SID1). Soaking the BmN4-SID1 in dsRNA corresponding to endogenous target genes induced a significant decrease of the amount of mRNA or protein. A small amount of dsRNA was enough to silence the target gene in a few days. Overexpression of CeSID-1 did not affect the cell viability. Our results suggest that BmN4-SID1 can be used in many applications in silkworm cells and will become a valuable resource for gene analysis.

Adverse events associated with intraocular injections of bevacizumab in eyes with neovascular glaucoma.

BACKGROUND: Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has been reported to cause rapid regression of anterior segment neovascularization in eyes with neovascular glaucoma when administered intraocularly. Several studies have reported the safety profile of intravitreal injections of bevacizumab in patients with various retinal pathologies. We investigated the occurrence of adverse events associated with intraocular bevacizumab injections in patients with neovascular glaucoma. METHODS: We retrospectively reviewed the charts of 84 eyes of 70 patients with neovascular glaucoma that received intraocular bevacizumab injections to treat anterior segment neovascularization for the first time at Kanazawa University Hospital. RESULTS: The mean age of the patients was 63.5 ± 13.3 years (± standard deviation; range, 31-85 years). The underlying retinal diseases were proliferative diabetic retinopathy in 58 eyes (69%), central retinal vein occlusion in 17 eyes (20%), ocular ischemic syndrome in four eyes (5%), central retinal artery occlusion in three eyes (4%), branch retinal vein occlusion in one eye (1%), and radiation retinopathy in one eye (1%). The total number of intraocular injections of bevacizumab was 116 (1.4 ± 0.8 injections/eye, range, one to five injections/eye). Most were intravitreal injections (1.25 mg/0.05 ml; 115 injections, 99%). No cases had marked inflammation, lens injuries, marked vitreous hemorrhage, retinal detachment, or endophthalmitis. However, two eyes (2%) of two cases (3%) developed central retinal artery occlusion 3 or 4 days after bevacizumab injection. Both were among four eyes (i.e., 50%) with ocular ischemic syndrome. One of them had received an intracameral injection of bevacizumab (0.75 mg/0.03 ml) before the adverse event. No cases experienced systemic side-effects including myocardial infarction and cerebrovascular accidents within 3 months after bevacizumab injection. CONCLUSIONS: Central retinal artery occlusion may be a relatively common complication following intraocular injection of anti-VEGF agents in patients with neovascular glaucoma, particularly when it was associated with ocular ischemic syndrome. Since visual prognosis of central retinal artery occlusions is usually poor, intraocular injection of anti-VEGF agents should be performed with thoughtful consideration of the risks and benefits of the treatment, and with a strict follow-up examination, especially in high-risk patients.

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.

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.

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.

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.

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.