Age prediction using fundus parameters of normal eyes from the Kumejima population study.

PURPOSE: Artificial intelligence can predict the age of an individual using color fundus photographs (CFPs). This study aimed to investigate the accuracy of age prediction in the Kumejima study using fundus parameters and to clarify age-related changes in the fundus. METHODS: We used nonmydriatic CFPs obtained from the Kumejima population study, including 1,646 right eyes of healthy participants with reliable fundus parameter measurements. The tessellation fundus index was calculated as R/(R + G + B) using the mean value of the red-green-blue intensity in eight locations around the optic disc and foveal region. The optic disc ovality ratio, papillomacular angle, and retinal vessel angle were quantified as previously described. Least absolute shrinkage and selection operator regression with leave-one-out cross-validation was used to predict age. The relationship between the actual and predicted ages was investigated using Pearson's correlation coefficient. RESULTS: The mean age of included participants (834 males and 812 females) was 53.4 ± 10.1 years. The mean predicted age based on fundus parameters was 53.4 ± 8.9 years, with a mean absolute error of 3.64 years, and the correlation coefficient between actual and predicted age was 0.88 (p < 0.001). Older patients had greater red and green intensities and weaker blue intensities in the peripapillary area (p < 0.001). CONCLUSIONS: Age could be predicted using the CFP parameters, and there were notable age-related changes in the peripapillary color intensity. The age-related changes in the fundus may aid the understanding of the mechanism of fundus diseases such as age-related macular degeneration.

Sex determination using color fundus parameters in older adults of Kumejima population study.

PURPOSE: Deep learning artificial intelligence can determine the sex using only fundus photographs. However, the factors used by deep learning to determine the sex are not visible. Therefore, the purpose of the study was to determine whether the sex of an older individual can be determined by regression analysis of their color fundus photographs (CFPs). METHODS: Forty-two parameters were analyzed by regression analysis using 1653 CFPs of normal subjects in the Kumajima study. The parameters included the mean values of red, green, and blue intensities; the tessellation fundus index; the optic disc ovality ratio; the papillomacular angle; and the retinal vessel angles. Finally, the L2 regularized binomial logistic regression was used to predict the sex using all the parameters, and the diagnostic ability was assessed through the leave-one-cross-validation. RESULTS: The mean age of the 838 men and 815 women were 52.8 and 54.0 years, respectively. The ovality ratio and retinal artery angles in women were significantly smaller than that in men. The green intensity at all locations for the women were significantly higher than that of men (P < 0.001). The discrimination accuracy rate assessed by the area-under-the-curve was 80.4%. CONCLUSIONS: Our methods can determine the sex from the CFPs of the adult with an accuracy of 80.4%. The ovality ratio, retinal vessel angles, tessellation, and the green intensities of the fundus are important factors to identify the sex in individuals over 40 years old.

Factors Threatening Central Visual Function of Patients with Advanced Glaucoma: A Prospective Longitudinal Observational Study.

PURPOSE: To identify risk factors for further deterioration of central visual function in advanced glaucoma eyes. DESIGN: Prospective, observational 5-year study. PARTICIPANTS: Advanced glaucoma patients with well-controlled intraocular pressure (IOP), mean deviation (MD) of the Humphrey Field Analyzer (HFA) 24-2 program ≤-20 dB and best-corrected visual acuity (BCVA) of 20/40. METHODS: The HFA 10-2 test and BCVA examination were performed every 6 months, and the HFA 24-2 test was performed every 12 months for 5 years. The Cox proportional hazards model was used to identify risk factors for deterioration of HFA 10-2 and 24-2 results and BCVA. MAIN OUTCOME MEASURES: Deterioration of HFA 10-2 results was defined by the presence of the same ≥3 points with negative total deviation slope ≤-1 dB/year at P < 0.01 on ≥3 consecutive tests, deterioration of HFA 24-2 results by an increase ≥2 in the Advanced Glaucoma Intervention Study score on ≥2 consecutive tests, and deterioration of BCVA by an increase of ≥0.2 logarithm of the minimum angle of resolution (logMAR) on ≥2 consecutive tests. RESULTS: A total of 175 eyes of 175 patients (mean age, 64.1 years; mean baseline IOP, 13.2 mmHg; mean BCVA, 0.02 logMAR; mean HFA 24-2 and 10-2 MD, -25.9 and -22.9 dB, respectively) were included. The probabilities of deterioration in HFA 10-2 and 24-2 results and BCVA were 0.269 ± 0.043 (standard error), 0.173 ± 0.031, and 0.194 ± 0.033, respectively, at 5 years. Lower BCVA at baseline (P = 0.012) was associated significantly with further deterioration of HFA 10-2 results. Better HFA 24-2 MD (P < 0.001) and use of systemic antihypertensive agents (P = 0.009) were associated significantly with further deterioration of HFA 24-2 results, and a greater ß-peripapillary atrophy area-to-disc area ratio (P < 0.001), use of systemic antihypertensive agents (P = 0.025), and lower BCVA (P = 0.042) were associated significantly with further deterioration of BCVA, respectively. CONCLUSIONS: In advanced glaucoma eyes with well-controlled IOP, BCVA, ß-peripapillary atrophy area-to-disc area ratio, and use of systemic antihypertensive agents were significant prognostic factors for further deterioration of central visual function.

Effects of optic nerve head-related parameters on retinal vessel calibers measurement results on fundus photographs.

BACKGROUND: Although relationship between the retinal vessel caliber (RVC) and glaucoma is well known, there has been a paucity of information on the effects of glaucoma-related optic nerve head (ONH) structural factors on the RVC. Information on this relationship should be useful in studying possible roles of ocular circulation in the development and progression of glaucoma. METHOD: Subjects were from Kumejima Study participants aged 40 years and older in Kumejima, Japan. Normal subjects and eyes were defined according to standardized systemic and ocular examinations. The central retinal artery and vein equivalents (CRAE and CRVE) were determined on fundus photographs by correcting the magnification using the refractive error, corneal curvature, and axial length (AL) of an individual eye and paraxial ray tracing; the ONH structural parameters were determined by planimetry. RESULTS: In a total of 558 right eyes (558 normal subjects), aged 49.0 ± 7.1 (standard deviation) years with gradable photographs and planimetric results, CRAE averaged 136.1 ± 12.3 µm and CRVE 216.9 ± 17.4 µm. After adjustment for the effects of confounding factors in multivariate analysis, the AL (P < 0.001), rim area (P = 0.019), disc area (P = 0.042), and smoking (P = 0.035-0.043) correlated positively, and the mean blood pressure (P < 0.001) negatively with CRAE; the AL (P < 0.001), rim area (P = 0.001), disc area (P = 0.005), smoking (P < 0.001), and male sex (P = 0.013) correlated positively, and the ß-peripapillary atrophy (ß-PPA) area (P = 0.044), vertical Cup/Disc ratio (v-C/D) (P = 0.035), and age (P < 0.001) negatively with CRVE. CONCLUSION: The current study showed significant effects of rim area, v-C/D or ß-PPA area determined on the photographs on the RVC measurement results. Further, it showed a necessity to incorporate the glaucoma-related ONH structural parameters as co-variables to correctly estimate the effects of various factors on the RVC.

Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.0×10-8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.

Factors Associated with Progression of Japanese Open-Angle Glaucoma with Lower Normal Intraocular Pressure.

PURPOSE: To characterize the natural history and define the risk factors associated with the progression of normal-tension glaucoma (NTG) in Japanese patients who were followed up closely without treatment. DESIGN: Prospective 5-year study. PARTICIPANTS: Patients with NTG with intraocular pressure (IOP) consistently ≤15 mmHg without treatment at baseline. METHODS: Visual field (VF) examinations were performed every 3 months, and disc/peripapillary retina photographs were taken every 6 months. Patients were followed up without treatment. MAIN OUTCOME MEASURES: Deterioration in VF was defined by reference to Guided Progression Analysis Software of the Humphrey VF Swedish Interactive Thresholding Algorithm 24-2 (Carl Zeiss Meditec, Jena, Germany) and disc/peripapillary retina deterioration as adjudged by 3 independent observers. Life table analysis was used for evaluating the time to disease progression, as defined by VF or deterioration of the optic nerve head structure. The Cox proportional hazards model was used to identify risk factors for glaucoma progression. RESULTS: We enrolled 90 patients (mean age, 53.9 years; baseline IOP, 12.3 mmHg; mean deviation [MD], -2.8 decibels [dB]). The MD slope averaged -0.33 dB/year (median, -0.23; 95% confidence interval [CI], -0.44 to -0.22). Glaucoma progression probability at 5 years was 66% (95% CI, 55-78), as defined by VF deterioration or disc/peripapillary retina deterioration (criterion 1): 52% (95% CI, 37-60), as defined by VF deterioration (criterion 2), and 50% (95% CI, 38-71), as defined by disc/peripapillary retina deterioration (criterion 3). Presence or history of disc hemorrhage (DH) (P < 0.001), long-term IOP fluctuation (P = 0.020), and a greater vertical cup-to-disc ratio (v-C/D) (P = 0.018) were significant predictors for progression defined by criterion 1. Long-term IOP fluctuation (P = 0.011) and a greater v-C/D (P = 0.036) were significant predictors for progression by criterion 2. Presence or history of DH (P = 0.0018) and long-term IOP fluctuation (P = 0.022) were significant predictors for progression by criterion 3. CONCLUSIONS: In Japanese patients with NTG with mean baseline IOP of 12.3 mmHg without treatment, estimated mean MD slope for 5 years was -0.33 dB/year; probability of glaucoma progression based on VF or disc/peripapillary end points at 5 years was 66%. Presence or history of DH, long-term IOP fluctuation, and greater v-C/D significantly contributed to progression.

Differences of body height, axial length, and refractive error at different ages in Kumejima study.

PURPOSE: To determine the relationships between the axial length (AL), refractive error (RE), and body height (BH) at different ages of a genetically-stable population in Kumejima, Japan. METHODS: Cross-sectional, population-based study. Residents of Kumejima who were ≥ 40-years old were studied. The eligible residents had a thorough ocular examinations including measurements of the AL, RE, and BH. The subjects were divided into decade groups. The relationships between the AL, the RE, and the BH of the different decades were determined. RESULTS: Reliable measurements of the AL of the right eyes were obtained from 2198 (1103 men and 1095 women) normal subjects. There was a significant and negative correlation between the age and the BH (r = -0.44, P < 0.001) and the AL (r = -0.27, P < 0.001). There were significant and positive correlations between the BH and AL in all subjects (r = 0.38, P < 0.001). There was a significant and positive correlation between the BH and the AL in all age brackets (r = 0.26~0.49, P < 0.001). There was a significant and positive correlation between the age and RE (spherical equivalent; r = 0.49, P < 0.001). There were significant and negative correlations between the BH and RE in all subjects (r = -0.29, P < 0.001). CONCLUSIONS: The younger individuals tend to be taller, have longer AL, and are more myopic. Considering the marked improvement of the nutritional status during the growth period of each generation and its close association with BH, nutrition may be one of factors that is related to the increase in the prevalence of myopia in the younger generation.

A nationwide survey of factors influencing adherence to ocular hypotensive eyedrops in Japan.

INTRODUCTION: Few reports have investigated the status of adherence in Japan on a large scale. We aimed to investigate the status of adherence to topical glaucoma treatment and its associated factors. METHODS: A nationwide survey was conducted as a prospective fashion. Participants in this survey were subjects with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension or pseudoexfoliation glaucoma who had been prescribed anti-glaucoma ophthalmic eyedrops and whose ophthalmologist considered prescribing any fixed combination of ocular hypotensive eyedrops for the first time between 2011 and 2012. Subjects and their attending ophthalmologists independently completed a questionnaire by utilizing a fixed combination of ocular hypotensive eyedrops. RESULTS: A total of 1358 ophthalmologists from 1071 medical institutions participated in this survey. We registered 4430 subjects (2049 males and 2381 females). In total, data from 3853 subjects (87.6%) were analyzed after inclusion of subjects based on inclusion and exclusion criteria. Good adherence was defined as not forgetting instillation during the past week. Rates of good adherence reported by subjects and ophthalmologists were 72.4 and 78.5%, respectively (P < 0.0001). The consistency of adherence evaluation between subjects and ophthalmologists was moderate [kappa score 0.5025 (95% confidence interval 0.4740-0.5309)]. Significant factors associated with adherence were size of clinic, age, gender, number of types of ocular hypotensive eyedrops, ease of instillation, preferred number of eyedrops, preferred frequency of instillation of eyedrops, and knowledge of glaucoma. CONCLUSION: Adherence to ocular hypotensive eyedrops among Japanese subjects was relatively good. Concordance of adherence between subjects' reports and ophthalmologists' responses was moderate. Size of clinic, number of types of ocular hypotensive eyedrops, ease of instillation, preferred number of eyedrops, preferred frequency of instillation of eyedrops, and knowledge of glaucoma were associated with adherence among Japanese glaucoma subjects.

Optic Disc Margin Anatomic Features in Myopic Eyes with Glaucoma with Spectral-Domain OCT.

PURPOSE: To investigate optic disc margin anatomic features in myopic eyes with open-angle glaucoma (OAG) using spectral-domain (SD) OCT. DESIGN: Cross-sectional study. PARTICIPANTS: Two hundred four eyes of 102 participants with OAG and 106 eyes of 53 participants without glaucoma with axial length of 24 mm or more. METHODS: Radial SD OCT B-scans centered on the optic discs were acquired in each eye, and the SD OCT data were colocalized with the optic disc stereophotographs. Optic disc margin anatomic features were evaluated as (1) SD OCT structure coinciding with the disc margin identified in the stereophotograph, (2) border tissue configuration, and (3) presence of Bruch's membrane overhang, and their frequency was computed in each clock-hour position. Further, paired eyes of myopic participants with OAG were divided into eyes with better or worse visual field defect (VFD), according to the mean deviation of the Humphrey visual field test, and associated factors were compared. MAIN OUTCOME MEASURES: Spectral-domain OCT structures coinciding with the visible optic disc margin in stereophotographs. RESULTS: In myopic eyes with OAG, mean axial length was 25.96±1.07 mm and mean deviation was -8.87±7.78 dB. In approximately 90% of the participants, anterior scleral opening (ASO) coincided with the temporal disc margin and Bruch's membrane opening (BMO) with the nasal disc margin. Border tissue configuration was externally oblique in the temporal region and internally oblique in the nasal region of the optic disc. Bruch's membrane overhang was observed in a relatively small percentage of eyes. The same pattern of disc margin anatomic features was observed in the myopic eyes without glaucoma. The myopic optic disc was shaped by the temporal shifting of the BMO from the ASO, and the extent of shifting was expressed as the width of γ zone parapapillary atrophy (PPA). The greater γ zone PPA width was associated significantly with the worse VFD between paired eyes. CONCLUSIONS: The myopic eyes with OAG exhibited characteristic optic disc margin anatomic features that was considered to be derived from myopic deformation of the eye. The greater γ zone PPA width may increase susceptibility to the glaucomatous stress.

Multiple Temporal Lamina Cribrosa Defects in Myopic Eyes with Glaucoma and Their Association with Visual Field Defects.

PURPOSE: To investigate characteristics of lamina cribrosa (LC) defects in myopic eyes with open-angle glaucoma (OAG) using spectral-domain (SD) optical coherence tomography (OCT). DESIGN: Cross-sectional study. PARTICIPANTS: One hundred thirty-three eyes with OAG and 83 eyes without OAG, with axial length of 24 mm or more. METHODS: Serial enhanced depth imaging SD OCT B-scans of the optic disc were acquired and reviewed for LC defects (diameter, ≥100 µm) and large pores (diameter, 60-100 µm). The numbers and locations of LC defects and large pores in each eye were assessed. In eyes with OAG, factors related to the number of LC defects were evaluated, as well as the association between the locations of LC defects and visual field (VF) defects (e.g., paracentral scotoma [PCS] and superior or inferior hemifield defects). MAIN OUTCOME MEASURES: Numbers and locations of LC defects and large pores. RESULTS: In myopic eyes with and without OAG, the average numbers of LC defects were 3.8 and 0.8 and numbers of large pores were 1.9 and 1.6, respectively. In both groups, LC defects and large pores were located predominantly at the temporal periphery. Among eyes with OAG, the number of LC defects was relatively high in the eyes with greater optic disc tilt angle and worse mean deviation of the VF (both P < 0.001). The number of temporal LC defects and tilt angle were associated with presence of PCS, whereas the number of inferior and superior LC defects and torsion direction were associated with presence of superior and inferior VF defects. CONCLUSIONS: Myopic eyes with OAG exhibited LC defects and large pores at similar locations as those without OAG, but in greater numbers, suggesting that these focal alternations of the LC in myopic eyes may evolve into larger defects when glaucoma develops in the eye. The number of LC defects, which was related to the optic disc tilt angle, was associated significantly with glaucomatous VF defects in both severity and location. This suggests that myopia may influence glaucomatous VF defects through optic disc tilt by way of an increased number of LC defects at the temporal periphery.

Vertical asymmetry of lamina cribrosa tilt angles using wide bandwidth, femtosecond mode-locked laser OCT; effect of myopia and glaucoma.

PURPOSE: Morphological features of the lamina cribrosa (LC) and optic disc may be important in the pathogenesis of glaucoma and myopic neuropathy. We therefore performed a cross-sectional study of patients with glaucoma and myopic neuropathy to evaluate vertical asymmetry of LC tilt angles (LCTAs) from Bruch's membrane opening (BMO). MATERIAL AND METHODS: Forty-six control eyes and 35 primary open-angle glaucoma (POAG) eyes were included. A raster scanning protocol with 300 single B-scans (without averaging) were obtained using optical coherence tomography with a wide-bandwidth, femtosecond mode-locked (ML) laser. Superior temporal to inferior nasal (ST) direction and inferior temporal to superior nasal (IT) direction (±45° rotation with a horizontal line) lines were drawn, and the angle between the inner edge of the BMO plane and the best fitting line for the anterior LC plane was measured as the LCTA. The generalized estimating equation was used to analyze the eye-derived data. RESULTS: Although no significant differences in either ST-LTCAs or IT-LTCAs were observed between the glaucoma group and non-glaucoma group, the IT-LCTAs were found to be significantly greater than the ST-LCTA in both the glaucoma and non-glaucoma groups (P < 0.001). After adjustment for other potential confounding factors by multivariate analysis, greater refractive errors were significantly correlated with IT-LCTAs. CONCLUSIONS: Vertical asymmetry of the LC tilting from the BMO plane exists in both normal and POAG eyes, and correlates with the degree of myopia.

Detecting Preperimetric Glaucoma with Standard Automated Perimetry Using a Deep Learning Classifier.

PURPOSE: To differentiate the visual fields (VFs) of preperimetric open-angle glaucoma (OAG) patients from the VFs of healthy eyes using a deep learning (DL) method. DESIGN: Cohort study. PARTICIPANTS: One hundred seventy-one preperimetric glaucoma VFs (PPGVFs) from 53 eyes in 51 OAG patients and 108 healthy eyes of 87 healthy participants. METHODS: Preperimetric glaucoma VFs were defined as all VFs before a first diagnosis of manifest glaucoma (Anderson-Patella's criteria). In total, 171 PPGVFs from 53 eyes in 51 OAG patients and 108 VFs from 108 healthy eyes in 87 healthy participants were analyzed (all VFs were tested using the Humphrey Field Analyzer 30-2 program; Carl Zeiss Meditec, Dublin, CA). The 52 total deviation, mean deviation, and pattern standard deviation values were used as predictors in the DL classifier: a deep feed-forward neural network (FNN), along with other machine learning (ML) methods, including random forests (RF), gradient boosting, support vector machine, and neural network (NN). The area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of discrimination for each method. MAIN OUTCOME MEASURES: The AUCs obtained with each classifier method. RESULTS: A significantly larger AUC of 92.6% (95% confidence interval [CI], 89.8%-95.4%) was obtained using the deep FNN classifier compared with all other ML methods: 79.0% (95% CI, 73.5%-84.5%) with RF, 77.6% (95% CI, 71.7%-83.5%) with gradient boosting, 71.2% (95% CI, 65.0%-77.5%), and 66.7% (95% CI, 60.1%-73.3%) with NN. CONCLUSIONS: Preperimetric glaucoma VFs can be distinguished from healthy VFs with very high accuracy using a deep FNN classifier.

Current Status of Glaucoma-related Data Management and Efforts toward Data Standardization.

Purpose: ï¼·e conducted a survey to evaluate the current status of glaucoma-related medical data management and standardization, aiming to improve the development of glaucoma care and research in Japan. Materials and methods: The survey was performed as a paper-based questionnaire of 14 universities that both participate in the glaucoma-related data standardization committee, established by the Japan Glaucoma Society in 2014, and actively perform glaucoma care. Results: All enrolled university hospitals installed an electronic hospital information system and used any of three ophthalmology-limited electronic chart systems. However, only 30.8% of the hospitals established a data extraction system from an electronic medical chart system, and only 14.3% could practically apply medical data for secondary research purposes. In all, 35.7% of the hospitals operate a medical cooperation system with local medical institutions and 42.9% electronically managed medical data inside their departments. Conclusion: This survey clarified the current state of medical data management and standardization.

Three-dimensional optic nerve head images using optical coherence tomography with a broad bandwidth, femtosecond, and mode-locked laser.

PURPOSE: The aim of this study was to demonstrate the fine laminar structure of the optic nerve head (ONH), in vivo, using a broad wavelength, ultra-high resolution, and optically coherent tomography (OCT) system. METHODS: This high-resolution OCT system, based on a 200 nm bandwidth spectrometer and an 8 femtosecond ultra-short, mode-locked, coherent laser light source, enabled in vivo cross-sectional ONH imaging with 2.0 µm axial resolution. A total of 300 optic disc B-scans, which consisted of 300 × 2048 pixels, were obtained in 10 µm steps. Three-dimensional images were rendered from these images to obtain n face images of the optic disc. Fundus photography, scanning laser ophthalmoscopy (SLO), and standard OCT were also performed for all subjects. RESULTS: Thirty-six eyes of normal subjects and ten eyes of glaucoma patients with mean age of 40.0 ± 10.0 years were enrolled in this study. Sequential en face images, from the ONH surface to deeper layers, were reconstructed in 2.0 µm steps. Observation of the images indicated variations in the shape and arrangement of the lamina pores at different depths. Clear lamina pores were identified by this technique in 44 eyes, compared with the fundus camera (identified in six eyes), SLO (identified in 14 eyes), and standard OCT (identified in 24 eyes) (all comparisons, p < 0.001). CONCLUSIONS: The fine structure of the ONH could be resolved in vivo using our OCT, providing improved imaging that can be used in research and clinical applications for a better characterization of the anatomical and pathological features associated with glaucoma.

Hyperbaric pressure and increased susceptibility to glutamate toxicity in retinal ganglion cells in vitro.

PURPOSE: To investigate the effect of hyperbaric pressure on purified retinal ganglion cells (RGCs) and the additive effect of hyperbaric pressure on glutamate-induced RGC death. METHODS: An RGC primary culture from 8-day-old Wistar rats was prepared and cultured in a hyperbaric chamber. The RGC survival rate under various pressure conditions and with 5 or 25 µM of glutamate stimulation was determined and compared with that of RGCs under isobaric conditions. First, RGCs were cultured at atmospheric pressure (0 mmHg) and under hyperbaric pressure (+30 and +90 mmHg, with pressure fluctuations varying from 0 to +30 or +60 mmHg). Next, RGCs were cultured at +15, +30, and +90 mmHg with the addition of 5 or 25 µM of glutamate. The effects of N-Methyl-D-aspartic acid (NMDA) and 2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid (AMPA)/kainate receptor antagonists, MK-801, and 6,7-dinitroquinoxaline-2,3-dione (DNQX), on cell survival were assessed. Additionally, types of cell death and the induction of Bcl-2-associated X protein (BAX) leading to apoptosis were studied under hyperbaric pressure conditions and/or with 5 µM of glutamate. RESULTS: RGC death was not induced under increasing or fluctuating pressure conditions. RGC death was induced by 25 µM of glutamate and increased as pressure increased. RGC death was not induced by 5 µM of glutamate but was induced by and increased with increasing pressure. MK-801 and DNQX significantly reduced glutamate-induced RGC death, and DNQX was more effective than MK-801. Under hyperbaric pressure conditions, the addition of 5 µM of glutamate resulted in the induction of apoptosis and BAX, which did not occur under hyperbaric pressure conditions or with the addition of glutamate alone. CONCLUSION: In a rat RGC culture, hyperbaric pressure alone did not induce RGC death but increased RGC susceptibility to glutamate toxicity, which may be of relevance to ocular diseases with pressure-induced RGC death.

Primary open-angle glaucoma in a population associated with high prevalence of primary angle-closure glaucoma: the Kumejima Study.

PURPOSE: To evaluate the prevalence of and risk factors for primary open-angle glaucoma (POAG) in a rural population of southwestern Japan. DESIGN: Population-based cross-sectional study. PARTICIPANTS: All residents 40 years of age and older in Kumejima, Okinawa, Japan. METHODS: Of the eligible 4632 residents 40 years of age and older, 3762 subjects (participant rate, 81.2%) underwent screening examinations, including visual acuity (VA) measurement, slit-lamp examination, Goldmann applanation tonometry, gonioscopy, undilated stereoscopic fundus photographs, autorefractometry, noncontact specular microscopy, pachymetry, and visual field (VF) testing using frequency-doubling technology. If glaucoma or other related ocular disorders were suspected, subjects were referred for definitive examinations including VF testing with the Humphrey Field Analyzer. The diagnosis of POAG was based on the criteria of the International Society for Geographical and Epidemiological Ophthalmology. MAIN OUTCOME MEASURES: Prevalence and risk factors of POAG. RESULTS: The prevalence of POAG was 4.0% (95% confidence interval [CI], 3.4%-4.7%); 82% of patients had an intraocular pressure (IOP) less than 22 mmHg, resulting in a prevalence of 3.3% (95% CI, 2.8%-3.9%). Because of POAG, 3 subjects had a VA worse than 20/400 in only 1 eye, and 1 subject had VA loss of worse than 20/400 bilaterally. The average IOP values (mean ± standard deviation) were 14.9 ± 3.2 and 14.6 ± 3.3 mmHg in the right and left eyes, respectively; the IOP values were higher in patients with POAG (15.4 ± 3.3 and 15.2 ± 3.3 mmHg, respectively) than in subjects without glaucoma (14.8 ± 3.1 and 14.4 ± 3.1 mmHg, respectively; P<0.045, Student t test). Multivariate analysis showed that male gender (P = 0.003), older age (P<0.001), higher IOP (P<0.001), longer axial length (P<0.001), and thinner central cornea (P = 0.006) were associated with POAG. CONCLUSIONS: High prevalence rates of POAG (4.0%) and POAG with normal IOP levels (3.3%), which were comparable with those on the Japanese mainland, were found in a southwestern rural island of Japan, where the prevalence of primary angle-closure glaucoma (previously reported as 2.2%) was considerably higher than on the Japanese mainland (0.6% in the Tajimi Study) or other countries. The risk factors for POAG included male gender, older age, higher IOP, myopia, and a thinner cornea.

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.

Correlation of magnetic resonance imaging optic nerve parameters to optical coherence tomography and the visual field in glaucoma.

BACKGROUND: To determine the viability of using magnetic resonance imaging measurement of optic nerve morphology as an objective analysis of glaucomatous damage. DESIGN: Retrospective study conducted at Tohoku University Hospital. PARTICIPANTS: Thirty-eight eyes of 19 patients with open-angle glaucoma. METHODS: Patients were scanned with T2-weighted and 3-T diffusion tensor magnetic resonance imaging, and parameters of the optic nerve, including fractional anisotropy, apparent diffusion coefficient and cross-sectional area, were determined. Conventional parameters of glaucomatous damage, including circumpapillary and macular retinal nerve fibre layer thickness, and mean deviation and average total deviation of the central 16 test points from the Humphrey Field Analyzer, were then compared with the magnetic resonance imaging-derived parameters. Spearman's coefficient of correlation was calculated to determine the significance of the correlation. MAIN OUTCOME MEASURE: Correlation coefficient between the magnetic resonance imaging parameters and the parameters of glaucomatous damage. RESULTS: Mean deviation was significantly correlated with all magnetic resonance imaging parameters (fractional anisotropy: r = 0.53, apparent diffusion coefficient: r = -0.44, cross-sectional area: r = 0.70). Circumpapillary retinal nerve fibre layer thickness was significantly correlated with fractional anisotropy (r = 0.60) and cross-sectional area (r = 0.47), but not apparent diffusion coefficient (r = -0.29). Central macular function and macular retinal nerve fibre layer thickness were also significantly correlated with magnetic resonance imaging parameters. CONCLUSIONS: Optic nerve magnetic resonance imaging parameters were significantly correlated to glaucomatous damage. Magnetic resonance imaging analysis of the optic nerve may, thus, have value as an objective instrument to assess glaucomatous degeneration, including the function of the macula.

Factors associated with visual field or structure progression occurring first in a prospective study on patients with untreated open-angle glaucoma with normal intraocular pressure.

BACKGROUND/OBJECTIVES: To identify factors associated with disc/retina deterioration in stereo fundus photographs preceding that of the visual field (VF), as determined with a Humphrey Field Analyzer (HFA) (Structure First deterioration) and factors associated with the latter preceding the former (Field First deterioration) in open-angle glaucoma (OAG) with lower normal intraocular pressure (IOP). SUBJECTS/METHODS: Prospective cohort study. Ninety eyes of 90 patients with OAG and a baseline IOP < 15 mmHg participated in a 5-year prospective study without treatment. IOP measurements and HFA 24-2 Swedish Interactive Test Algorithm Standard tests were performed every 3 months, and fundus photographs were obtained every 6 months. VF deterioration was determined by Guided Progression Analysis and deterioration of disc/retina was determined on stereophotographs by an independent committee. A multivariable Cox proportional hazard model was used to identify factors associated with Structure First deterioration, and with Field First deterioration. RESULTS: The average baseline age and mean deviation were 53.9 ± 9.8 years and -2.8 ± 2.8 dB, respectively. During the 5-year follow-up, the probability of Field First deterioration was 49% ± 6.6% (standard error) and that of Structure First deterioration was 33% ± 6.4% (P = 0.062, log-rank test). Disc hemorrhage (DH) prior to the event (P = 0.006) was associated with Structure First deterioration, and older age was associated with Field First deterioration (P = 0.040). CONCLUSIONS: In OAG eyes with lower normal IOP, DH was significantly associated with Structure First deterioration, and age was significantly associated with Field First deterioration.