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.

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.

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.

[Initial scotomas in normal tension glaucoma].

PURPOSE: To investigate risk factors for initial visual field pattern in normal tension glaucoma (NTG). PATIENTS AND METHODS: We studied 107 subjects, who underwent 24-2 or 30-2 Swedish interactive threshold algorithm standard visual fields as part of a multicenter study of newly diagnosed NTG patients. Only the eyes with initial parafoveal scotoma (IPFS) or initial nasal step (INS) Were included. IPFS was defined as a glaucomatous visual field (VF) defect in 1 hemifield (≥ 3 adjacent points with p < 5% within the central 10 degrees of fixation, ≥ 1 point with p < l% lying at the innermost paracentral points, and no VF abnormality outside the central 10 degrees). INS was defined in 1 hemifield (≥ 3 adjacent points with p < 5% in the nasal periphery outside 10 degrees of fixation, the nasal- most point with p < 1%, and no VF abnormality within the central 10 degrees). Clinical characteristics were compared between the 2 groups. RESULTS: Mean untreated intraocular pressure (IOP) (14.0 ± 1.3 vs. 16.0 ± l.4 mmHg; p = 0.0102) was significantly lower in patients with an IPFS than in patients with an INS. There were no significant differences in age (p = 0.6487) or spherical equivalent (p = 0.7561). CONCLUSION: Initial visual field pattern of NTG is influenced by untreated IOP level.

Aging-associated changes of optical coherence tomography-measured ganglion cell-related retinal layer thickness and visual sensitivity in normal Japanese.

PURPOSE: To report aging-associated change rates in circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and macular ganglion cell-inner plexiform layer and complex thickness (MGCIPLT, MGCCT) in normal Japanese eyes and to compare the data in linear scaled visual field (VF) sensitivity of central 4 points of Humphrey Field Analyzer (HFA) 24-2 test (VF4TestPoints) to that in MGCIPLT in four 0.6-mm-diameter circles corresponding to the four central points of HFA 24-2 adjusted for retinal ganglion cell displacement (GCIPLT4TestPoints). STUDY DESIGN: Prospective observational study METHODS: HFA 24-2 tests and spectral-domain optical coherence tomography (SD-OCT) measurements of cpRNFLT, MGCIPLT, MGCCT and GCIPLT4TestPoints were performed every 3 months for 3 years in 73 eyes of 37 healthy Japanese with mean age of 50.4 years. The time changes of SD-OCT-measured parameters and VF4TestPoints were analyzed using a linear mixed model. RESULTS: The aging-associated change rates were -0.064 µm/year for MGCIPLT and and -0.095 for MGCCT (P=0.020 and 0.017), but could not be detected for cpRNFLT. They accelerated with aging at -0.009µm/year/year of age for MGCIPLT (P<0.001), at 0.011 for MGCCT (P<0.001) and at 0.013 for cpRNFLT(0.031). The aging-associated decline of -82.1 [1/Lambert]/year of VF4TestPoints corresponded to -0.095 µm/year of GCIPLT4TestPoints. CONCLUSION: We report that aging-associated change rates of cpRNFLT, MGCIPLT and MGCCT in normal Japanese eyes were found to be significantly accelerated along with aging. Relationship between VF sensitivity decline rates and SD-OCT measured GCIPLT decline rates during physiological aging in the corresponding parafoveal retinal areas are also documented.

Relationship between fundus sex index obtained using color fundus parameters and body height or axial length in the Kumejima population.

PURPOSE: To investigate the relationship between the fundus sex index obtained from fundus photographs and body height or axial length in the Kumejima population. STUDY DESIGN: Prospective cross-sectional observational population study. METHODS: Using color fundus photographs obtained from the Kumejima population, 1,653 healthy right eyes with reliable fundus parameter measurements were included in this study. The tessellation fundus index was calculated as R/(R + G + B) using the mean value of the red-green-blue intensity in the 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. The masculine or feminine fundus was quantified using machine learning (L2 regularized binominal logistic regression and leave one out cross validation), with the range of 0-1 as the predictive value, and defined as the fundus sex index. The relationship between the fundus sex index and body height or axial length was investigated using Spearman's correlation. RESULTS: The mean age of the 838 men and 815 women included in this study was 52.8 and 54.0 years, respectively. The correlation coefficient between fundus sex index and body height was - 0.40 (p < 0.001) in all, 0.01 (p = 0.89) in men, and - 0.04 (p = 0.30) in women, and that between fundus sex index and axial length was - 0.23 (p < 0.001) in all, - 0.12 (p < 0.001) in men, and - 0.13 (p < 0.001) in women. CONCLUSION: This study shows that a larger number of masculine fundi tend to have longer axial lengths in each sex group. However, sex index was not significantly related with body height either in men or in women.

Predicting the Extent of Damage in the Humphrey Field Analyzer 24-2 Visual Fields Using 10-2 Test Results in Patients With Advanced Glaucoma.

Purpose: To predict Humphrey Field Analyzer 24-2 test (HFA 24-2) results using 10-2 results. Methods: A total of 175 advanced glaucoma eyes (175 patients) with HFA 24-2 mean deviation (MD24-2) of < -20 dB were prospectively followed up for five years using HFA 10-2 and 24-2 (twice and once in a year, respectively). Using all the HFA 24-2 and 10-2 test result pairs measured within three months (350 pairs from 85 eyes, training dataset), a formula to predict HFA 24-2 result using HFA 10-2 results was constructed using least absolute shrinkage and selection operator regression (LASSO). Using 90 different eyes (testing dataset), the absolute differences between the actual and LASSO-predicted MD24-2 and that between the slopes calculated using five actual and LASSO-predicted MD24-2 values, were adopted as the prediction error. Similar analyses were performed for the mean total deviation values (mTD) of the superior (or inferior) hemifield [hemi-mTDsup.24-2(-hemi-mTDinf.24-2)]. Results: The prediction error for the LASSO-predicted MD24-2 and its slope were 2.98 (standard deviation [SD] = 1.90) dB and 0.32 (0.33) dB/yr, respectively. The LASSO-predicted hemi-mTDsup.24-2 (hemi-mTDinf.24-2), and its slope were 3.02 (2.89) and 3.76 (2.72) dB, and 0.37 (0.41) and 0.44 (0.38) dB/year, respectively. These prediction errors were within two times SD of repeatability of the simulated stable HFA 24-2 VF parameter series. Conclusions: HFA 24-2 results could be predicted using the paired HFA 10-2 results with reasonable accuracy using LASSO in patients with advanced glaucoma. Translational Relevance: It is useful to predict HFA24-2 test from HFA10-2 test, when the former is not available, in advanced glaucoma.

Comparative Analysis of 24-2C, 24-2, and 10-2 Visual Field Tests for Detecting Mild-Stage Glaucoma With Central Visual field Defects.

PURPOSE: This study sought to identify the most effective testing program for detecting visual-field defects in mild-stage glaucoma with central visual-field defects. DESIGN: A multicenter, retrospective diagnostic testing evaluation. PARTICIPANTS: The study involved 93 eyes (83 patients) with mild-stage glaucoma (median mean deviation [interquartile range]: -1.79 [2.16] dB) with central visual-field defects and 69 eyes (63 patients; median mean deviation, -1.38 [2.31] dB) with mild-stage glaucoma without central visual-field defects, from Jikei University School of Medicine and Tajimi Iwase Eye Clinic. METHODS: Patients underwent 10-2 Swedish Interactive Thresholding Algorithm (SITA) Standard, 24-2 SITA Standard, and 24-2C SITA Faster tests. Central visual-field defects were defined using 10-2 SITA Standard and optical coherence tomography (OCT). A detection power of 4 points in the 24-2 that coincided with 10-2 (Center4), 12 points that lie within 10° (24-2-12), and 22 points that lie within 10° of 24-2C (24-2C-22) were analyzed using receiver operating characteristic (ROC) curves based on logistic regression analysis, using total deviation (TD) and pattern deviation (PD) probability plots. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC) of the Center4, 24-2-12, and 24-2C-22 tests. RESULTS: In the upper-central visual field, AUCs of the TD plot were 0.50 (0.40-0.58) for the Center4, 0.75 (0.67-0.83) for 24-2-12, and 0.85 (0.78-0.91) for 24-2C-22, with 24-2C-22 AUC significantly exceeding 24-2-12 AUC. For the PD plot, AUCs were 0.53 (0.44-0.63), 0.81 (0.74-0.89), and 0.84 (0.77-0.90), respectively. In the lower-central visual field, using a total plot, AUCs were 0.27 (0.18-0.36), 0.57 (0.47-0.69), and 0.57 (0.46-0.68) for the Center4, 24-2-12, and 24-2C-22, respectively. Using the PD plot in the upper field, AUCs were 0.27 (0.19-0.36), 0.64 (0.53-0.75), and 0.81 (0.72-0.90), respectively, with the AUC of the 24-2C-22 significantly exceeding that of 24-2-12. The 24-2C test was significantly faster than both the 24-2 and 10-2 tests, reducing testing duration by 46% and 52%, respectively. CONCLUSIONS: The 24-2C SITA Faster test is highly effective and efficient for detecting mild-stage glaucoma with central visual-field defects. This, and its reduced duration, makes it a valuable tool in clinical settings.

Effect of magnification error and axial length on circumpapillary capillary density and retinal nerve fiber layer thickness.

This study aimed to evaluate the effect of magnification error and axial length (AL) on circumpapillary capillary density (cpCD) and circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in healthy eyes. Seventy-two healthy eyes of 72 subjects with AL 24.7 ± 1.5 mm (range: 20.9-28.0 mm) were enrolled in this retrospective cross-sectional study and underwent optical coherence tomography angiography scanning. Magnification corrected measurement areas were obtained using AL upon which corrected cpCD, cpRNFLT values were determined. Relationships between AL and the percentage difference between corrected and uncorrected values (ΔcpCD, ΔcpRNFLT) as well as the effect of AL on magnification corrected cpCD, cpRNFLT were evaluated. ΔcpCD significantly increased with AL in the global, inferior nasal and superior nasal sectors (all p < 0.001). ΔcpRNFLT significantly increased with AL in global and all sectors (all p < 0.001) and the correlations were significantly stronger than that of ΔcpCD-AL in all sectors (all p < 0.001). Corrected cpCD did not associate with AL while corrected cpRNFLT demonstrated a significant positive association with AL in the global (p = 0.005) and temporal sector (p < 0.001). Magnification error led to a significant underestimation of cpCD in eyes with longer AL although its underestimation and the effect of AL was smaller in comparison to that of cpRNFLT.

Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.

Association of Bergmeister Papilla and Deep Optic Nerve Head Structures With Prelaminar Schisis of Normal and Glaucomatous Eyes.

PURPOSE: To investigate factors associated with the severity of prelaminar schisis (PLS) in heathy subjects and glaucoma patients. DESIGN: Prospective cross-sectional study. METHODS: A total of 217 eyes of 217 subjects (110 normal eyes and 107 open angle glaucoma eyes) were studied. Frequency and severity of PLS were compared between normal and glaucomatous eyes. Multivariate logistic models were used to assess factors associated with the severity of PLS. Factors considered were age, axial length, glaucomatous damage indices, Bruch membrane opening (BMO) and anterior scleral canal opening parameters, tractional forces (posterior vitreous staging and presence of Bergmeister papilla), circumpapillary choroidal thickness, lamina cribrosa (LC) parameters, and peripapillary scleral (PPS) angle. RESULTS: The frequency of PLS was 70.9% in normal eyes and 72.0% in glaucomatous eyes. There was no difference in frequency and severity between the groups. The presence of Bergmeister papilla was the strongest predictor of a more severe PLS in both normal and glaucomatous eyes (odds ratio [OR] + 9.78, 12.5; both P < .001). A larger PPS angle in normal eyes (OR = 1.19; P = .003) and a larger BMO area and a deeper LC depth in glaucomatous eyes (OR = 1.08, 1.05; both P = .038) were associated with severity of PLS. CONCLUSIONS: The severity of PLS was strongly associated with the presence of Bergmeister papilla, suggesting a traction-related phenomenon. Correlation of PLS severity with larger BMO area and deeper LC depth, which are optic nerve head structures associated with glaucoma, suggested its possible relationship with glaucomatous damage.

Differences in Factors Associated With Glaucoma Progression With Lower Normal Intraocular Pressure in Superior and Inferior Halves of the Optic Nerve Head.

Purpose: The purpose of this study was to investigate risk factors for progression in the superior and inferior hemi-visual fields (hemi-VFs) and the corresponding hemi-disc/retinas in eyes with normal tension glaucoma (NTG). Methods: A 5-year prospective follow-up of 90 patients with NTG with untreated intraocular pressure (IOP) consistently ≤ 15 mm Hg was conducted. The IOP and Humphrey Perimeter measurements and disc/retina stereo-photographs were taken every 3 and 6 months, respectively. Risk factors for progression in the superior and inferior hemi-VFs and in the superior and inferior hemi-disc/retinas were investigated. Results: The mean total deviation values decreased at -0.50 ± 0.76 and -0.13 ± 0.34 dB/year in the superior and inferior hemi-VFs, respectively (P < 0.001). In the superior hemi-VF, the risk factor for faster progression was greater long-term IOP fluctuation (P = 0.022). In the inferior hemi-VF, the risk factors were disc hemorrhage (DH), greater myopic refraction, body mass index (BMI), and vertical cup-to-disc ratio (v-C/D; P < 0.05). The progression probability was 47.7 ± 6.0 and 17.7 ± 4.7% at 5 years in the superior and inferior hemi-disc/retinas respectively (P < 0.001), and DH was a risk factor for progression in both (P = 0.001). Conclusions: In NTG eyes, greater BMI, myopia, and v-C/D are characteristic risk factors for faster progression in the superior half of the optic nerve head (ONH), whereas long-term IOP fluctuation is the significant risk factor in the inferior half of the ONH, whereas DH is a risk factor in both. Translational Relevance: Different risk factors were identified in superior and inferior hemifields in NTG eyes.