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.

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.

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.

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.

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.

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.

Phase 3 Clinical Trial Comparing the Safety and Efficacy of Netarsudil to Ripasudil in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: Japan Rho Kinase Elevated Intraocular Pressure Treatment Trial (J-ROCKET).

INTRODUCTION: A clinical trial evaluated ocular hypotensive efficacy and safety of netarsudil 0.02% once daily (QD) relative to ripasudil 0.4% twice daily (BID). METHODS: This was a single-masked, randomized, phase 3, superiority study. Japanese patients were randomized to either the netarsudil 0.02% group or the ripasudil 0.4% group in a 1:1 ratio and treated for 4 weeks. The primary efficacy variable was mean diurnal intraocular pressure (IOP) (average of diurnal time points at 09:00, 11:00, and 16:00) at Week 4. RESULTS: A total of 245 patients were included in the primary analysis. At Week 4, least squares (LS) mean of diurnal IOP adjusted for baseline was 15.96 and 17.71 mmHg in the netarsudil 0.02% and ripasudil 0.4% groups, respectively, demonstrating the superiority of netarsudil 0.02% QD over ripasudil 0.4% BID by a margin of - 1.74 mmHg (p < 0.0001). Mean reduction from baseline in mean diurnal IOP at Week 4 was 4.65 and 2.98 mmHg, respectively. Adverse events (AEs) occurred less frequently in netarsudil 0.02% than in ripasudil 0.4%, with the incidence of ocular AEs being 59.8% and 66.7%, respectively. The most frequently reported AE was conjunctival hyperemia in both groups, with an incidence of 54.9% and 62.6%, respectively. No serious eye-related AEs were reported. CONCLUSION: Netarsudil ophthalmic solution 0.02% dosed QD (p.m.) was well tolerated and more effective in reducing IOP than ripasudil ophthalmic solution 0.4% dosed BID. Netarsudil 0.02% QD may become an important option for the treatment of Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04620135.

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.

Neuroprotective effect of the calcium channel blocker nilvadipine on retinal ganglion cell death in a mouse ocular hypertension model.

We investigated whether nilvadipine has a neuroprotective effect on retinal ganglion cells (RGCs) in a mouse model of ocular hypertension (OH) that expresses cyan fluorescein protein (CFP) in RGCs. OH was induced in the right eyes of Thy1-CFP transgenic mice using a laser. Nilvadipine or vehicle treatment began simultaneously with OH modeling and was administered intraperitoneally once daily for 8 weeks. Intraocular pressure (IOP) in both the laser- and non-treated eyes was measured weekly with the microneedle method, and calculations were performed to estimate the pressure insult in each eye. Using a retinal whole mount, the number of RGCs was counted at week 9. Laser-treated eyes showed a significant increase in IOP (p < 0.01), and the pressure insult did not differ between the drug-treated groups. Over time, laser treatment produced a significant decrease in the number of RGCs in the vehicle-treated groups, but this effect was attenuated by nilvadipine treatment. The pressure insult and RGC survival rate were significantly negatively correlated in the vehicle-treated group (y = -0.078 x + 107.8, r = 0.76, p < 0.001), but not in the nilvadipine-treated group (y = -0.015 x + 99.9, r = 0.43, p = 0.128). Nilvadipine was a potent neuroprotective agent for RGCs in our mouse model of OH and may have potential for protection against glaucoma. This model is useful as a screening tool for drugs with retinal protective effects.

Deep Optic Nerve Head Structures Associated With Increasing Axial Length in Healthy Myopic Eyes of Moderate Axial Length.

PURPOSE: To elucidate which swept-source optical coherence tomography (OCT)-derived optic nerve head (ONH) parameters are associated with longer axial length (AXL) in healthy myopic eyes. DESIGN: Prospective cross-sectional observational study. METHODS: Two hundred eleven healthy eyes of 140 participants (96 emmetropic-mild myopic [AXL: 22.2-24.5 mm], 83 moderately myopic [24.5-26.0 mm], and 32 highly myopic [26.0-27.4 mm] eyes) were enrolled. Bruch membrane opening (BMO), anterior scleral canal opening (ASCO) area and ovality, minimum rim width, parameters defining misalignment between the BMO and ASCO planes, OCT-defined region of perineural canal retinal epithelium atrophy and externally oblique choroidal border tissue, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), circumpapillary choroidal thickness (cpChT), lamina cribrosa parameters, and peripapillary scleral (PPS) angle were calculated from BMO-centered radial scans reconstructed from 3D raster scans. Multivariate linear mixed models were used to elucidate ONH parameters that are independently associated with AXL. RESULTS: Longer AXL was associated with a greater misalignment between ASCO and BMO planes, larger region of externally oblique choroidal border tissue, thinner cpChT, larger PPS angle, larger ASCO area, and thicker cpRNFLT (all P < .040 after Bonferroni's correction for number of included explanatory variables). CONCLUSIONS: A greater misalignment between BMO and ASCO planes, thinner choroid, a more posteriorly bowed PPS, an enlargement of ASCO, and thicker cpRNFLT were each associated with longer AXL. An enhanced understanding of these AXL-associated configurations should provide essential information to improve our ability to detect glaucoma-induced ONH morphology in myopic eyes.

Genetic variants associated with glaucomatous visual field loss in primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is characterized by a progressive optic neuropathy with visual field loss. To investigate the genetic variants associated with visual field loss in POAG, Japanese POAG patients (n = 426) and control subjects (n = 246) were genotyped for 22 genetic variants predisposing to POAG that can be classified into those associated with intraocular pressure (IOP) elevation (IOP-related genetic variants) and optic nerve vulnerability independent of IOP (optic nerve-related genetic variants). The genetic risk score (GRS) of the 17 IOP-related and five optic nerve-related genetic variants was calculated, and the associations between the GRS and the mean deviation (MD) of automated static perimetry as an indicator of the severity of visual field loss and pattern standard deviation (PSD) as an indicator of the focal disturbance were evaluated. There was a significant association (Beta = - 0.51, P = 0.0012) between the IOP-related GRS and MD. The severity of visual field loss may depend on the magnitude of IOP elevation induced by additive effects of IOP-related genetic variants. A significant association (n = 135, Beta = 0.65, P = 0.0097) was found between the optic nerve-related, but not IOP-related, GRS and PSD. The optic nerve-related (optic nerve vulnerability) and IOP-related (IOP elevation) genetic variants may play an important role in the focal and diffuse visual field loss respectively. To our knowledge, this is the first report to show an association between additive effects of genetic variants predisposing to POAG and glaucomatous visual field loss, including severity and focal/diffuse disturbance of visual field loss, in POAG.

Identifying central 10° visual subfield associated with future worsening of visual acuity in eyes with advanced glaucoma.

BACKGROUND/AIMS: To determine a cluster of test points: visual subfield (VSF) of Humphrey Field Analyzer 10-2 test (HFA 10-2) of which baseline sensitivities were associated with future worsening of visual acuity (VA) in eyes with advanced glaucoma. METHODS: A total of 175 advanced glaucoma eyes of 175 advanced glaucoma patients with well controlled intraocular pressure (IOP), a mean deviation of the Humphrey Field Analyzer 24-2 (HFA 24-2) test ≤ -20 decibels and best corrected VA ≥20/40, were included. At baseline, HFA 24-2 and HFA 10-2 tests were performed along with VA measurements. All patients underwent prospective follow-up of 5 years, and VA was measured every 6 months. The Cox proportional hazards model was used to identify visual field sensitivities associated with deterioration of VA and also blindness. RESULTS: Deterioration of VA and blindness were observed in 15.4% and 3.4% of the eyes, respectively. More negative total deviation (TD) values in the temporal papillomacular bundle VSF were significantly associated with deterioration in VA. Averages of the TD values in this area of the HFA 10-2 test had the most predictive power of future VA deterioration (OR: 0.92, p<0.001). A very similar tendency was observed for blindness. CONCLUSION: In advanced glaucoma eyes with well-controlled IOP, careful attention is needed when the mean TD values in the temporal papillomacular bundle VSF, measured with a HFA 10-2 test is deteriorated. TD values of this VSF indicate higher risks for future deterioration of VA and also blindness.

Prevalence of Glaucoma and Its Systemic Risk Factors in a General Japanese Population: The Hisayama Study.

Purpose: To estimate the prevalence of glaucoma and its risk factors in a Japanese community. Methods: This study included 3405 Japanese community dwellers who were ≥40 years of age and enrolled in the Hisayama Study. This population-based, cross-sectional study was conducted from 2017 to 2018. A glaucoma screening test was performed using stereo fundus images and swept-source optical coherence tomography. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. Results: The prevalence of glaucoma was 7.6% (95% confidence interval [CI], 6.7-8.6) overall. The prevalence of primary open-angle glaucoma (POAG) was 5.8% (95% CI, 5.0-6.6); that of primary angle-closure glaucoma (PACG) was 0.7% (95% CI, 0.5-1.1); and that of exfoliation glaucoma was 1.1% (95% CI, 0.7-1.4). In addition to aging, lower estimated glomerular filtration rate (eGFR) (odds ratio [OR] = 1.15; 95% CI, 1.02-1.33), higher intraocular pressure (OR = 1.06; 95% CI, 1.01-1.12), longer axial length (OR = 1.44; 95% CI, 1.31-1.59), and thinner central corneal thickness (CCT) (OR = 1.09; 95% CI, 1.04-1.15) were significant risk factors for POAG. Diabetes (OR = 2.81; 95% CI, 1.19-6.62) was a significant risk factor for PACG, and diabetes (OR = 2.15; 95% CI, 1.03-4.47) and thinner CCT (OR = 1.14; 95% CI, 1.02-1.28) were significant risk factors for exfoliation glaucoma. Conclusions: The prevalence of glaucoma was approximately 8%, probably due to the increase in the Japanese aging population. Not only ocular factors but also lower eGFR for POAG and diabetes for PACG and exfoliation glaucoma were risk factors in a general Japanese population. Translational Relevance: Systemic factors such as eGFR and diabetes must also be considered when implementing preventive measures against glaucoma.

METTL23 mutation alters histone H3R17 methylation in normal-tension glaucoma.

Normal-tension glaucoma (NTG) is a heterogeneous disease characterized by retinal ganglion cell (RGC) death leading to cupping of the optic nerve head and visual field loss at normal intraocular pressure (IOP). The pathogenesis of NTG remains unclear. Here, we describe a single nucleotide mutation in exon 2 of the methyltransferase-like 23 (METTL23) gene identified in 3 generations of a Japanese family with NTG. This mutation caused METTL23 mRNA aberrant splicing, which abolished normal protein production and altered subcellular localization. Mettl23-knock-in (Mettl23+/G and Mettl23G/G) and -knockout (Mettl23+/- and Mettl23-/-) mice developed a glaucoma phenotype without elevated IOP. METTL23 is a histone arginine methyltransferase expressed in murine and macaque RGCs. However, the novel mutation reduced METTL23 expression in RGCs of Mettl23G/G mice, which recapitulated both clinical and biological phenotypes. Moreover, our findings demonstrated that METTL23 catalyzed the dimethylation of H3R17 in the retina and was required for the transcription of pS2, an estrogen receptor α target gene that was critical for RGC homeostasis through the negative regulation of NF-κB-mediated TNF-α and IL-1ß feedback. These findings suggest an etiologic role of METTL23 in NTG with tissue-specific pathology.

Risk factors for glaucoma are reflected in abnormal responses to frequency-doubling technology screening in both normal and glaucoma eyes.

The frequency-doubling technology (FDT) screening test (FDT-C-20-1) has adopted in many recent population-based glaucoma surveys, but factors associated with false-positive (FP) responses to FDT-C-20-1 in normal eyes and false-negative (FN) responses in glaucoma eyes were not known. These factors were investigated in a population-based setting using the data from 3805 normal eyes (2381 subjects) and 272 eyes with definite glaucoma (215 subjects) in the Kumejima Study participants with reliable FDT-C-20-1 results. Considering the presence of at least one abnormal test point (P < 0.01) as abnormal, the specificity and sensitivity of FDT-C-20-1 for glaucoma were 91.8% (95% confidence interval, 91.1 ~ 92.5) and 56.3% (47.0 ~ 62.5), respectively. Multivariate linear mixed-model logistic regression analysis showed correlations with older age, worse visual acuity, greater ß-peripapillary area (P < 0.001 for all comparisons) and more myopic refraction (P = 0.030) with the FP responses in normal eyes, and normal-tension glaucoma (P = 0.043), a better mean deviation value of Humphrey perimetry (P = 0.001), larger rim area (P = 0.041), and absence of disc hemorrhage (P = 0.015) with the FN responses in glaucoma eyes. In a population-based setting, abnormal responses to FDT-C-20-1 indicate the presence of a risk factor for glaucoma in normal eyes and risk factors for more rapid progression in glaucoma eyes.

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.

Differentiating Diagnosed and Undiagnosed Primary Angle-Closure Glaucoma and Open-Angle Glaucoma: A Population-Based Study.

PURPOSE: To study and compare factors contributing to the differentiation between diagnosed and undiagnosed primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) in the same population. DESIGN: Population-based survey. PARTICIPANTS: All residents 40 years of age and older in Kumejima, Japan. METHODS: Primary angle-closure glaucoma and POAG were diagnosed according to the criteria of the International Society of Geographical and Epidemiological Ophthalmology. Factors contributing significantly to the differentiation between diagnosed and undiagnosed PACG and POAG were selected from various systemic, ocular, visual function, and fundus planimetric parameters using multivariate logistic regression analysis and were compared between the two diseases. MAIN OUTCOME MEASURES: Factors contributing significantly to the differentiation between diagnosed and undiagnosed PACG and POAG. RESULTS: The prevalence rates of PACG and POAG were 2.2% and 4.0%, respectively. A greater proportion of patients with PACG (34.1%) received a diagnosis previously compared with patients with POAG (17.2%; P = 0.004). Worse mean deviation on visual field (VF) testing (odds ratio, 0.869; 95% confidence interval, 0.788-0.959; P = 0.006) and the presence of signs suggestive of previous acute angle closure (odds ratio, 4.35; range, 1.66-11.36; P = 0.003) contributed to a established diagnosis of PACG at the time of screening. A greater vertical cup-to-disc ratio (3.74; range, 1.38-10.17; P = 0.012) contributed with marginal significance to an established diagnosis of POAG at the time of screening. CONCLUSIONS: Primary angle-closure glaucoma was more likely to have been diagnosed previously than POAG during a screening examination. Examination of the anterior segment and VF may contribute more to the detection of PACG, and disc examination may contribute more to the detection of POAG.

The Inferior, Superior, Temporal Rim Width Pattern (IST Rule) Detects Glaucoma in a Japanese Population.

PRCIS: The inferior>superior>temporal rim width rate (IST pattern) rather than inferior≥superior≥nasal≥temporal (ISNT) pattern was suited for screening glaucoma in Japanese subjects. Failure of the IST pattern was associated with several important risk factors for glaucoma. PURPOSE: The purpose of this study was to find a rim width rate pattern to yield the highest positive likelihood ratio (LR+) in detecting glaucoma eyes and to identify risk factors for glaucoma correlating with its failure in a population-based setting. METHODS: Disc stereophotographs of 2474 eyes of 2474 normal subjects and 237 eyes of 237 glaucoma subjects found in the Kumejima Study were analyzed using computer-assisted planimetry. Among all combinations of the inferior (I), superior (S), nasal (N) and/or temporal (T) rim width rate, a pattern showing the highest LR+ was selected and risk factors for glaucoma correlating with its failure were determined using multiple logistic regression analysis. RESULTS: The average I, S, N, and T rim widths (SD) were 0.45 (0.10), 0.39 (0.09), 0.47 (0.11), and 0.27 (0.07) mm. Among all combinations, the I>S>T rim width rate pattern (IST pattern) disregarding the N rim width showed the highest LR+ of 2.002 (95% confidence interval, 1.778-2.253). Failure of the IST pattern in normal eyes correlated with a smaller disc area (P<0.001) and disc ovality (P=0.005) and larger ß-peripapillary area (P<0.001) and compliance with in glaucoma eyes with a smaller ß-PPA area (P=0.027), thicker central corneal thickness (P=0.017), lower intraocular pressure (P=0.019), and higher body mass index (P=0.037). CONCLUSION: Among all combinations, the I>S>T rim width pattern, the IST pattern, yielded the highest LR+ in detecting glaucoma in Japanese glaucoma eyes and its failure of or compliance with the pattern significantly correlated with several known risk factors for glaucoma.