A Case of Personal Identification Via Postmortem Computed Tomography Confirmation of Aphakic Eyes.

Postmortem computed tomography (PMCT) is used commonly in forensic medicine. Postmortem computed tomography of the head provides information on the eyes and orbits and may reveal intraocular abnormalities. We present a case in which the identity of a deceased man was confirmed by the presence of aphakic eyes detected on PMCT. A decomposed body was found in a house and suspected to be a man in his 40s who lived alone. Autopsy identified pontine hemorrhage as the cause of death. Although signs of previous dental treatment were evident, the storage period of the householder's dental records had expired. He had no family members to provide DNA for a comparative DNA analysis. Postmortem computed tomography before autopsy revealed aphakia (ie, the absence of eye lenses) suggestive of previous ocular surgery. His medical records revealed that he had undergone ocular surgery for secondary glaucoma due to uveitis, which had resulted in artificial aphakia. Peripheral iridectomy scars fully matched the findings in his medical records, thus identifying the body. The unusual finding of artificial aphakia in a man in his 40s facilitated the personal identification in this case. In conclusion, PMCT provides additional information, and the correct interpretation of intraocular PMCT findings by forensic pathologists is crucial.

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.

Epidemiologic and Clinical Characteristics of Optic Neuritis in Japan.

PURPOSE: To elucidate the clinical and epidemiologic characteristics of optic neuritis in Japan. DESIGN: Multicenter cross-sectional, observational cohort study. PARTICIPANTS: A total of 531 cases of unilateral or bilateral noninfectious optic neuritis identified in 33 institutions nationwide in Japan. METHODS: Serum samples from patients with optic neuritis were tested for anti-aquaporin-4 antibodies (AQP4-Abs) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) using a cell-based assay and were correlated with the clinical findings. MAIN OUTCOME MEASURES: Antibody positivity, clinical and radiologic characteristics, and visual outcome. RESULTS: Among 531 cases of optic neuritis, 12% were AQP4-Ab positive, 10% were MOG-Ab positive, 77% were negative for both antibodies (double-negative), and 1 case was positive for both antibodies. Pretreatment visual acuity (VA) worsened to more than a median 1.0 logarithm of the minimum angle of resolution (logMAR) in all groups. After steroid pulse therapy (combined with plasmapheresis in 32% of patients in AQP4-Ab-positive group), median VA improved to 0.4 logMAR in the AQP4-Ab-positive group, 0 logMAR in the MOG-Ab-positive group, and 0.1 logMAR in the double-negative group. The AQP4-Ab-positive group showed a high proportion of females, exhibited diverse visual field abnormalities, and demonstrated concurrent spinal cord lesions on magnetic resonance imaging (MRI) in 22% of the patients. In the MOG-Ab-positive group, although posttreatment visual outcome was good, the rates of optic disc swelling and pain with eye movement were significantly higher than those in the AQP4-Ab-positive and double-negative groups. However, most cases showed isolated optic neuritis lesions on MRI. In the double-negative group, 4% of the patients had multiple sclerosis. Multivariate logistic regression analysis of all participants identified age and presence of antibodies (MOG-Ab and AQP4-Ab) as significant factors affecting visual outcome. CONCLUSIONS: The present large-scale cohort study revealed the clinicoepidemiologic features of noninfectious optic neuritis in Japan. Anti-aquaporin-4 antibody-positive optic neuritis has poor visual outcome. In contrast, MOG-Ab positive cases manifested severe clinical findings of optic neuritis before treatment, but few showed concurrent lesions in sites other than the optic nerve and generally showed good treatment response with favorable visual outcome. These findings indicate that autoantibody measurement is useful for prompt diagnosis and proper management of optic neuritis that tends to become refractory.

Long-term regular exercise and intraocular pressure: the Hisayama Study.

PURPOSE: To investigate the association between long-term regular exercise (exercise frequency and exercise time) and 5-year changes in intraocular pressure in a general Japanese population. METHODS: This population-based, cohort study was conducted in 2007. A total of 3119 Japanese community dwellers aged ≥ 40 years underwent eye examinations including intraocular pressure measurement with a noncontact tonometer. Of these, 1871 subjects (801 men and 1070 women) who underwent intraocular pressure measurement in 2012 participated. We assessed the associations of exercise frequency and exercise time with intraocular pressure using a linear regression model, adjusted for age and possible risk factors that can affect intraocular pressure. RESULTS: The mean 5-year intraocular pressure change ± standard deviation was - 0.84 ± 1.9 mmHg. After adjustment for age, sex, systolic blood pressure, diabetes, total cholesterol, high-density lipoprotein cholesterol, body mass index, waist circumference, smoking habit, alcohol intake, work intensity levels, and intraocular pressure at baseline, we observed that increased exercise frequency (times/week) and increased exercise time (min/week) were both significantly associated with reduced intraocular pressure (p < 0.05 each). In the subgroup analyses based on the presence/absence of possible confounding risk factors, there was no evidence of heterogeneity among all subgroups (p for heterogeneity > 0.2). CONCLUSIONS: Increased exercise frequency levels and increased exercise time are both independently associated with reduced intraocular pressure levels after adjustment for confounding factors.

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.

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.

Structure and function of the interphotoreceptor matrix surrounding retinal photoreceptor cells.

The interphotoreceptor matrix (IPM) is a highly organized structure with interconnected domains surrounding cone and rod photoreceptor cells and extends throughout the subretinal space. Based on known roles of the extracellular matrix in other tissues, the IPM is thought to have several prominent functions including serving as a receptor for growth factors, regulating retinoid transport, participating in cytoskeletal organization in surrounding cells, and regulation of oxygen and nutrient transport. In addition, a number of studies suggest that the IPM also may play a significant role in the etiology of retinal degenerative disorders. In this review, we describe the present knowledge concerning the structure and function of the IPM under physiological and pathological conditions.

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.

Choroidal Thickness Increases During Parasympathetic Dominance After Immersion of the Foot in Warm Water.

PURPOSE: This study aimed to assess the course of changes in choroidal morphology after immersion of the foot in warm water at 40°C using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: Forty-three right eyes of 43 healthy participants were included. Changes in choroidal morphology were determined using EDI-OCT to evaluate subfoveal choroidal thickness (SCT). Systolic, diastolic, and mean blood pressures (SBP, DBP, and MBP, respectively) were also measured to determine systemic circulatory dynamics at baseline, immediately after immersion (0 min), and 10, 20, and 30 min after immersion. RESULTS: Immediately after immersion, SBP, DBP, and MBP were significantly declined versus baseline. In contrast, the SCT was significantly increased after warm water immersion. However, all these parameters did not change significantly compared to the baseline within 30 min. CONCLUSION: In the normal eye, parasympathetic nerve activity induced by warming stimuli increases choroidal morphology in response to a decrease in systemic circulatory activity, which normalizes within 30 min. The findings of this study may provide basic data for the prevention and treatment of various choroidal diseases in which sympathetic hyperactivity is involved in the pathogenesis.

Changes in Retinal Hemodynamics in the Optic Nerve Head of Healthy Participants Measured Using Laser Speckle Flowgraphy after a Cold Pressor Test.

PURPOSE: Autoregulation of retinal vessels is stronger than that of choroidal vessels. This study aimed to use laser speckle flowgraphy to determine the time course of changes in retinal hemodynamics of healthy eyes after a cold pressor test. METHODS: This prospective study included 44 right eyes of 44 healthy volunteers (age, 21.7 ± 5.0 years). The mean blur rate, which is a quantitative index of the relative blood flow velocity in the retina, was measured using laser speckle flowgraphy. The vessel average of mean blur rate at the optic nerve head, intraocular pressure, systolic blood pressure, diastolic blood pressure, mean blood pressure, heart rate, and ocular perfusion pressure were evaluated at baseline, immediately after the cold pressor test, and 10, 20, and 30 minutes after the test. RESULTS: Immediately after the test (0 minutes), systolic blood pressure, diastolic blood pressure, mean blood pressure, and ocular perfusion pressure were significantly increased compared with those at baseline; however, no changes were observed at 10, 20, and 30 minutes after the test. In contrast, intraocular pressure, heart rate, and the vascular mean blur rate values at the optic nerve head did not change throughout the course of the study. CONCLUSIONS: Sympathetic hyperactivity induced by the cold pressor test increased systemic circulatory dynamics, but not retinal circulatory hemodynamics, suggesting the involvement of vascular autoregulation.

Association between corneal hysteresis and glaucoma in a Japanese population: the Hisayama Study.

AIMS: To investigate the association between corneal hysteresis and the presence of glaucoma and its subtypes in a general Japanese population. METHODS: We analysed the data of 2338 Japanese community-dwellers aged ≥40 years (1059 men, 1279 women) who underwent an eye examination in 2018 as part of the population-based, cross-sectional Hisayama Study. Participants were divided into quartile levels of corneal hysteresis, which had been measured with an ocular response analyzer. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. We conducted a logistic regression analysis to determine the ORs and their 95% CIs for the presence of outcomes according to the corneal hysteresis quartiles. RESULTS: Glaucoma was diagnosed in 154 participants: primary open-angle glaucoma (POAG), n=115; primary angle-closure glaucoma, n=17; exfoliation glaucoma, n=21 and secondary glaucoma without exfoliation glaucoma, n=1. After adjustment for confounders, the OR for prevalent glaucoma was significantly increased in the participants in the first corneal-hysteresis quartile compared with those in the fourth quartile (OR: 1.80; 95% CI: 1.03 to 3.17). Regarding glaucoma subtypes, the first-quartile participants had significantly greater likelihoods of the presence of POAG (OR: 1.63; 95% CI: 1.02 to 2.61) and exfoliation glaucoma (OR: 6.49; 95% CI: 1.44 to 29.30) compared with those in the third and fourth quartiles after adjustment for potential confounders. CONCLUSIONS: These results demonstrated a significant inverse association between corneal hysteresis and the likelihood of glaucoma, suggesting that the measurement of corneal hysteresis would provide useful information for elucidating the aetiology of glaucoma.

Choroidal Morphology and Systemic Circulation Changes During the Menstrual Cycle in Healthy Japanese Women.

PURPOSE: Changes in systemic circulatory dynamics and choroidal thickness are poorly understood. This study aimed to investigate the time course of changes in choroidal morphology during normal menstrual cycles in healthy women using enhanced depth imaging optical coherence tomography (EDI-OCT). MATERIALS AND METHODS: This prospective study included 15 left eyes of 15 healthy Japanese women (mean age, 20.2 ± 0.8 years) with a normal menstrual cycle. Using EDI-OCT, the subfoveal choroidal thickness (SCT) was manually measured during the late follicular and mid-luteal phases. Intraocular pressure (IOP), systolic, diastolic, and mean blood pressure (SBP, DBP, and MBP), and heart rate (HR) were also evaluated during these phases. RESULTS: SBP, DBP, and MBP were significantly elevated in the mid-luteal phase. The average SCT was significantly decreased in the mid-luteal phase. In contrast, there were no significant changes in IOP or HR. CONCLUSION: These findings indicate that choroidal thickness decreases during the mid-luteal phase in healthy Japanese women with normal menstrual cycles depending on systemic circulatory dynamics. However, since the difference in the SCT values between the late follicular and the mid-luteal phase is not large (7 µm), the menstrual cycle may have little influence on the interpretation of choroidal thickness data in clinical practice.

Parasympathetic Dominance Decreases the Choroidal Blood Flow Velocity Measured Using Laser Speckle Flowgraphy.

BACKGROUND: This study aimed to examine the changes to choroidal blood flow velocity using laser speckle flowgraphy (LSFG) in healthy eyes after warm water immersion at 40°C. METHODS: Data regarding the right eyes of 23 healthy volunteers were included. The mean blur rate (MBR) of the macula, which represents the choroidal blood flow velocity, was evaluated using LSFG. Intraocular pressure (IOP), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), ocular perfusion pressure (OPP), and MBR were assessed at baseline, immediately after immersion (0 minutes), and 10, 20, and 30 minutes later. RESULTS: At 0 minutes, SBP, DBP, MBP, and OPP values were lower than those at baseline. The MBR significantly declined immediately after immersion to -6.0 ± 5.2%. However, there were no changes in these parameters after 10, 20, or 30 minutes. A significant positive correlation was observed between the MBR, SBP, DBP, MBP, and OPP values. In healthy individuals, the dominant parasympathetic activity induced by warm stimulation reduced the choroidal hemodynamic rate in the macula and decreased systemic circulatory dynamics, which normalized after 10 minutes. CONCLUSIONS: These findings suggest that the dominant parasympathetic activity induced by warm water immersion at 40°C may lead to a reduction in the systemic circulation rate and choroidal blood flow rate in the macula. These findings may help prevent and treat various retinal choroidal diseases, in which sympathetic hyperactivity is involved in the pathogenesis of the disease.

Changes in Choroidal Circulation Hemodynamics Measured Using Laser Speckle Flowgraphy after a Cold Pressor Test in Young Healthy Participants.

Using laser speckle flowgraphy (LSFG), we investigated the time course of changes in choroidal circulation hemodynamics after a cold pressor test in healthy eyes. This prospective study included the right eye of 19 young healthy participants. The macular mean blur rate (MBR) was measured with LSFG. The MBR, intraocular pressure (IOP), systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), mean blood pressure (MBP), and ocular perfusion pressure (OPP) were evaluated at baseline; immediately after the test and 10, 20, and 30 min later. Immediately after the test (0 min), SBP, DBP, MBP, and OPP were significantly elevated compared with those at baseline. The macular MBR significantly increased by +10.3 ± 7.1% immediately after the test. However, there was no change after 10, 20, and 30 min in the above parameter. A significant positive correlation of the macular MBR with the SBP, MBP, and OPP was observed. In young healthy individuals, increased sympathetic activity induced by a cold pressor test increases choroidal hemodynamics in the macula along with an increase in systemic circulatory dynamics, which normalizes after 10 min. Therefore, LSFG may provide a novel approach for assessing sympathetic activity and intrinsic vascular responsiveness in the eye.

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.

Changes in choroidal circulation hemodynamics during the menstrual cycle in young, healthy women.

PURPOSE: The current study aimed to investigate the time course of changes in choroidal circulation hemodynamics and their relationship to systemic circulation dynamics during the normal menstrual cycle in young, healthy women using laser speckle flowgraphy (LSFG). METHODS: This prospective study included 26 eyes from 13 young, healthy women (21.3 ± 4.0 years) with a normal menstrual cycle and 24 eyes from 12 young, healthy men (21.8 ± 4.4 years) as a control group. The macular mean blur rate (MBR), a quantitative index of relative blood flow velocity in the choroid, was measured using LSFG. MBR, intraocular pressure (IOP), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), and ocular perfusion pressure (OPP) were evaluated in the late follicular phase and mid-luteal phase in women and at baseline and 10 days after baseline in men, respectively. RESULTS: In the female group, IOP, SBP, DBP, MBP, and OPP values were significantly higher in the mid-luteal phase than those observed in the late follicular phase (P = 0.035, P < 0.001, P = 0.041, P = 0.001, P = 0.014, respectively). The average macular MBR values in the late follicular phase and mid-luteal phase were 12.7 ± 5.3 and 13.7 ± 6.6 (+7.7 ± 19.4%), representing a significant increase in the mid-luteal phase (P = 0.041). The rate of change in MBR exhibited a significant positive correlation with changes in DBP and MBP (R = 0.456, P = 0.019 and R = 0.474, P = 0.014). However, there were no significant changes in any of the factors in the male group during the study period. CONCLUSIONS: Our results suggest that in young, healthy women with a normal menstrual cycle, choroidal blood flow velocity decreases during the late follicular phase and increases during the mid-luteal phase, depending on systemic circulatory dynamics.

The Enantiomer of Allopregnanolone Prevents Pressure-Mediated Retinal Degeneration Via Autophagy.

In an ex vivo rat ocular hypertension (OHT) model, the neurosteroid allopregnanolone (AlloP) exerts neuroprotective effects via enhancement of both GABAA receptors and autophagy. We now examine whether its enantiomer (ent-AlloP), which is largely inactive at GABA receptors, offers similar neuroprotection in ex vivo and in vivo rat OHT models. Ex vivo rat retinal preparations were incubated in a hyperbaric condition (10 and 75 mmHg) for 24 h. An in vivo ocular hypertension (OHT) model was induced by intracameral injection of polystyrene microbeads. We examined pharmacological effects of AlloP, ent-AlloP, picrotoxin (a GABAA receptor antagonist), and 3-MA (an autophagy inhibitor) histologically and biochemically. We found that both AlloP and ent-AlloP have marked neuroprotective effects in the retina, but effects of the unnatural enantiomer are independent of GABAA receptors. Electron microscopic analyses show that pressure elevation significantly increased autophagosomes (APs) in the nerve fiber layer and addition of AlloP also increased APs and degenerative autophagic vacuoles (AVds). ent-AlloP markedly increased APs and AVds compared to AlloP. Examination of LC3B-II and SQSTM1 protein levels using immunoblotting revealed that AlloP increased LC3B-II, and ent-AlloP further enhanced LC3B-II and suppressed SQSTM1, indicating that autophagy is a major mechanism underlying neuroprotection by ent-AlloP. In an rat in vivo OHT model, single intravitreal ent-AlloP injection prevented apoptotic cell death of retinal ganglion cells similar to AlloP. However, even in this model, ent-AlloP was more effective in activating autophagy than AlloP. We conclude that ent-AlloP may be a prototype of potential therapeutic for treatment of glaucoma as an autophagy enhancer without affecting GABA receptors.

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.