Tractography optimization using quantitative T1 mapping in the human optic radiation.

Diffusion MRI tractography is essential for reconstructing white-matter projections in the living human brain. Yet tractography results miss some projections and falsely identify others. A challenging example is the optic radiation (OR) that connects the thalamus and the primary visual cortex. Here, we tested whether OR tractography can be optimized using quantitative T1 mapping. Based on histology, we proposed that myelin-sensitive T1 values along the OR should remain consistently low compared with adjacent white matter. We found that complementary information from the T1 map allows for increasing the specificity of the reconstructed OR tract by eliminating falsely identified projections. This T1-filtering outperforms other, diffusion-based tractography filters. These results provide evidence that the smooth microstructural signature along the tract can be used as constructive input for tractography. Finally, we demonstrate that this approach can be applied in a case of multiple sclerosis, and generalized to the HCP-available MRI measurements. We conclude that multimodal MRI microstructural information can be used to eliminate spurious tractography results in the case of the OR.

[Correlation of intraocular pressure variation after visual field examination with 24-hour intraocular pressure variations in primary open-angle glaucoma].

OBJECTIVES: We retrospectively examined intraocular pressure variations after visual field examination in primary open angle glaucoma (POAG), together with its influencing factors and its association with 24-hour intraocular pressure variations. SUBJECTS AND METHODS: Subjects were 94 eyes (52 POAG patients) subjected to measurements of 24-hour intraocular pressure and of changes in intraocular pressure after visual field examination using a Humphrey Visual Field Analyzer. Subjects were classified into three groups according to the magnitude of variation (large, intermediate and small), and 24-hour intraocular pressure variations were compared among the three groups. Factors influencing intraocular pressure variations after visual field examination and those associated with the large variation group were investigated. RESULTS: Average intraocular pressure variation after visual field examination was -0.28 ± 1.90 (range - 6.0(-) + 5.0) mmHg. No significant influencing factors were identified. The intraocular pressure at 3 a.m. was significantly higher in the large variation group than other two groups (p < 0.001). Central corneal thickness was correlated with the large variation group (odds ratio = 1.04; 95% confidence interval, 1.01-1.07 ; p = 0.02). CONCLUSION: No particular tendencies in intraocular pressure variations were found after visual field examination. Increases in intraocular pressure during the night might be associated with large intraocular pressure variations after visual field examination.

Association Between Days of the Week and Intraocular Pressure: Japan Ningen Dock Study.

PRCIS: The analysis of intraocular pressure (IOP) by day of the week using the mega database showed a periodic weekly pattern with the highest value on Monday. PURPOSE: To evaluate IOP by the day of the week. PATIENTS AND METHODS: Annual health checkup examinees between April 2014 and March 2015 were cross-sectionally evaluated. As a result, 655,818 participants [51.5±10.5 (range: 20-96) years, 40.1% women] from 103 medical centers were included. IOP was measured using a noncontact tonometer. The mean IOPs of each day of the week were compared using multiple comparison test and multiple linear regression analysis. Wednesday was set as the reference. Moreover, weekly IOP variations stratified by sex and age were also evaluated. RESULTS: Mean IOPs from Monday to Sunday were 13.19±2.97, 13.06±2.92, 13.05±2.91, 13.05±2.92, 13.12±2.94, 13.10±2.96, and 13.16±2.78 mm Hg. IOP was significantly higher on Monday, Friday, and Saturday than those on Wednesday ( P <0.001, <0.001, 0.002). After adjusting for factors affecting IOP, the IOPs on Monday and Saturday were higher than those on Wednesday [ß=0.097 (95% CI: 0.074-0.121), P <0.001; ß=0.032 (95% CI: 0.005-0.059), P =0.019]. Men had significantly higher IOPs on Monday and Saturday than on Wednesday [ß=0.142 (95% CI: 0.110-0.173), P <0.001; ß=0.053 (95% CI: 0.017-0.089), P =0.004], whereas women did not have a significant trend. Participants aged below 65 years had higher IOPs on Monday ( P <0.001 in under 60 years; P =0.003 in 60-64 years), while those aged 65 years or older did not ( P =0.856). CONCLUSION: IOP values may have a periodic weekly pattern. The high IOP on Monday was more pronounced in men aged less than 65 years.

Comparison of Glaucoma Detection Performance of Binocular Perimetry Screening Program Using imo Perimetry With Frequency Doubling Technology.

Purpose: We aimed to preliminarily compare the glaucoma detection accuracy of a head-mounted binocular visual perimeter "imo" screening program (ISP) with that of frequency doubling technology (FDT). Methods: This multicenter, diagnostic accuracy study based on prospectively collected data included 76 non-glaucoma (including pre-perimetric glaucoma) eyes and 92 glaucomatous eyes from patients visiting two hospitals. Patients underwent ISP and FDT (C-20-1 screening program) on the same day. Diagnostic efficacy was evaluated using receiver operating characteristic curves and areas under the curve (AUCs). In addition, we compared the ISP and FDT testing times. Results: AUC values for ISP versus FDT were as follows: (1) mild-stage glaucoma (mean deviation [MD] > -6 dB), 0.82 (95% confidence interval [CI], 0.75-0.88) versus 0.76 (95% CI, 0.68-0.83); moderate-stage glaucoma (-6 dB ≥ MD ≥ -12 dB), 0.98 (95% CI, 0.95-1.00) versus 0.96 (95% CI, 0.93-1.00); and advanced-stage glaucoma (-12 dB > MD), 1.00 (95% CI, 1.00-1.00) versus 0.99 (95% CI, 0.98-1.00). In addition, mild-stage glaucoma was classified into two stages (MD > -3 D) and (-3 D ≥ MD > -6 D). AUC values were 0.81 (95% CI, 0.73-0.88) versus 0.76 (95% CI, 0.68-0.84) for MD > -3 D and 0.86 (95% CI, 0.77-0.94) versus 0.73 (95% CI, 0.61-0.86) for -3 D ≥ MD > -6 D. The testing time for the ISP was significantly shorter than that of FDT for all glaucoma stages (P < 0.001). Conclusions: The ISP demonstrates non-inferiority in detecting glaucoma and has a shorter testing time compared with FDT. These findings provide evidence for applied further studies on large-scale population-based glaucoma screening. Translational Relevance: Our study provides a non-inferior and quicker glaucoma screening than existing tools.

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.

A Novel Visual Field Screening Program for Glaucoma With a Head-Mounted Perimeter.

PRCIS: A novel visual field screening program with a head-mounted perimeter 'imo' could detect glaucoma at all stages in a short time with high accuracy. PURPOSE: The present study aimed to examine the accuracy and availability of a novel glaucoma visual field screening program using a head-mounted visual perimeter 'imo.' PARTICIPANTS AND METHODS: Eyes of 76 non-glaucoma participants and 92 glaucoma patients were examined. All patients underwent visual field tests using the Humphrey Visual Field Analyzer (30-2 or 24-2 Swedish Interactive Thresholding Algorithm standard program) and imo (the visual field screening program). We evaluated five visual field screening program indicators: sensitivity, specificity, positive predictive value, negative predictive value, and testing time. We also evaluated the ability of this visual field screening program to differentiate between glaucoma patients and normal controls using the receiver operating characteristic curves and areas under the receiver operating characteristic curves. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of the visual field screening program were 76%-100%, 91%-100%, 86%-89%, and 79%-100%, respectively. The visual field screening program test time was 46±13 seconds for normal controls and 61±18, 82±21, and 105±16 econds, respectively for mild, moderate, and advanced-stage patients. The areas under the receiver operating characteristic curves were 0.77, 0.97, and 1.0 in the mild, moderate, and advanced stages, respectively. CONCLUSIONS: Visual field screening using a head-mounted perimeter 'imo' detected glaucoma at all stages in a short time with high accuracy.

Personality Traits Associated with Treatment Choice with an Explicit Statistical Prediction After an Explanation in a Negative Context: A Study in Patients with Glaucoma.

Purpose: Over 50% of patients with early-stage glaucoma discontinue topical therapy within the first 6 months of treatment initiation. This risk of discontinuation could be reduced by how the ophthalmologist explains the treatment plan. Ophthalmologists can explain the treatment plan to patients in either positive or negative contexts. Although explanations in a negative context can be selected depending on the medical situation, identification of patients who will choose the treatment with explicit statistical prediction after an explanation in a negative context is important; personality traits are related to these emotional decisions. Therefore, in the present study, we examined the personality traits associated with choice of treatment with explicit statistical prediction after an explanation in a negative context. Patients and Methods: A total of 147 patients with glaucoma were recruited for this study. The questionnaire booklets used contained positively framed or negatively framed versions of an "Asian disease problem" to enable examination of the influence of the way in which a problem is framed (framing effect) on the participants' decision-making. The Japanese version of the Ten-Item Personality Inventory was used to estimate the personality traits of the participants. Results: Low conscientiousness was identified as the only variable that was strongly predictive of the choice of treatment with explicit statistical prediction (ß = -0.44, z = 2.19, p = 0.03). In addition, while the association was not statistically significant, low neuroticism was found to be weakly predictive of the choice of uncertain treatment (ß = -0.37, z = 1.73, p = 0.08). Conclusion: In conclusion, we showed that low levels of conscientiousness predict the choice of treatment with explicit statistical prediction (ie, topical treatment) for glaucoma after an explanation in a negative context.

Age-related visual outcomes in eyes with diffractive multifocal intraocular lenses.

BACKGROUND/OBJECTIVES: To assess the influence of patient age on visual outcomes in eyes with diffractive multifocal intraocular lenses (IOLs) SUBJECTS/METHODS: Based on age, we classified eyes with diffractive multifocal IOL into four groups: u50 (under 50 years old), 50s (50-59 years), 60s, and 70s. Corrected distance (CD), distance-corrected near (DCN) visual acuity (VA), and defocus curve were measured postoperatively. Using an "area-of-focus" metric, the distant, intermediate, and near area-of-focus (AoF) were also measured. These postoperative results were compared between the age groups. RESULTS: At 3 months after surgery, the CDVA in the u50, 50s, 60s, and 70s groups were -0.18, -0.16, -0.14, and -0.10 logMAR, respectively. The 70s CDVA was significantly worse than the u50 and 50s groups (P = 0.002, P = 0.049). The DCNVA in the u50, 50s, 60s, and 70s were 0.01, 0.03, 0.03, and 0.08 logMAR. DCNVA in the 70s group was significantly worse than that in the u50 and 60s groups (P = 0.008 and P = 0.019, respectively). The near AoF was smaller in the 70s than in the u50 and 50s groups (P = 0.040, P = 0.047). In both the intermediate and distant AoFs, there was no significant difference between the four age groups. A steep decline in near AoF was observed in patients over 60 years of age. CONCLUSIONS: The CDVA, DCNVA, and near AoF declined with patient age in eyes with diffractive multifocal IOL. The near AoF showed a drastic decline over 60 years.

Multi-Contrast Magnetic Resonance Imaging of Visual White Matter Pathways in Patients With Glaucoma.

Purpose: Glaucoma is a disorder that involves visual field loss caused by retinal ganglion cell damage. Previous diffusion magnetic resonance imaging (dMRI) studies have demonstrated that retinal ganglion cell damage affects tissues in the optic tract (OT) and optic radiation (OR). However, because previous studies have used a simple diffusion tensor model to analyze dMRI data, the microstructural interpretation of white matter tissue changes remains uncertain. In this study, we used a multi-contrast MRI approach to further clarify the type of microstructural damage that occurs in patients with glaucoma. Methods: We collected dMRI data from 17 patients with glaucoma and 30 controls using 3-tesla (3T) MRI. Using the dMRI data, we estimated three types of tissue property metrics: intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (IsoV). Quantitative T1 (qT1) data, which may be relatively specific to myelin, were collected from all subjects. Results: In the OT, all four metrics showed significant differences between the glaucoma and control groups. In the OR, only the ICVF showed significant between-group differences. ICVF was significantly correlated with qT1 in the OR of the glaucoma group, although qT1 did not show any abnormality at the group level. Conclusions: Our results suggest that, at the group level, tissue changes in OR caused by glaucoma might be explained by axonal damage, which is reflected in the intracellular diffusion signals, rather than myelin damage. The significant correlation between ICVF and qT1 suggests that myelin damage might also occur in a smaller number of severe cases.

Age-Related Changes in Intraocular Pressure: Japan Ningen Dock Study.

PRCIS: The analysis of intraocular pressure by age using a mega database showed a consistent age-related intraocular pressure decrease. PURPOSE: To clarify the association between age and intraocular pressure (IOP), the IOP value by age was assessed using a large IOP database. MATERIALS AND METHODS: This cross-sectional study was conducted among 103 health checkup institutions registered to the Japan Society of Ningen Dock, and included participants who underwent annual health checkups between April 2014 and March 2015. The inclusion criteria were as follows: complete data for IOP in eyes, body mass index, waist circumference, blood pressure, hemoglobin A1c, and a self-administered health questionnaire. A total of 655,818 participants were enrolled. The mean age was 51.5±10.5 years (range, 20-96 y), and 40.1% were women. IOP was measured using a noncontact tonometer. Multiple linear regression analysis was conducted to explore factors associated with IOP, including age, and analyses stratified by age group: <40, 40-69, and ≥70 years. RESULTS: A consistent negative association between IOP and age [ß=-0.353 (95% confidence interval: -0.360--0.346)] was observed. In the age groups of <40 and ≥70 years, the age-related IOP decline was more pronounced [ß=-0.502 (95% CI: -0.566 to -0.439); ß=-0.674 (95% CI: -0.753 to -0.595)], with it being 14.21±2.95 and 11.18±2.52 mm Hg in the 20-24 and 90-96 year age groups, respectively. The middle-aged (aged 40-69 y) population showed gradual decline [ß=-0.313 (95% CI: -0.323 to -0.303)]. CONCLUSION: Age was strongly and negatively associated with IOP. The magnitude of IOP decline across lifespans was ∼3 mmHg. Age-related decreases in IOP were nonlinear and phasic.

Association between personality traits and experience of adverse periocular reactions to topical prostaglandin analogues.

BACKGROUND: Aesthetically unappealing adverse periocular reactions to prostaglandin (PG) eye-drops are a major challenge in glaucoma treatment. This study analysed the personality traits of patients with glaucoma based on a five-factor model and examined the associations between these factors and adverse periocular reactions. METHODS: One hundred and forty-seven patients with glaucoma were surveyed anonymously regarding their personality traits and how often adverse periocular reactions were experienced. RESULTS: The analysis included 117 valid responses (71 men and 46 women, age: 61.9±11.5 years). Patients who experienced hypertrichosis of the eyelashes scored significantly higher on extraversion (p<0.05), with no significant differences in the other four personality traits. Patients who experienced eyelid hyperpigmentation and deepening of the upper eyelid sulcus showed no significant differences in any of the personality traits. Younger patients scored significantly higher on hypertrichosis (p<0.05). CONCLUSION: The experience of adverse reactions differed according to patient age and personality traits. Therefore, eye-drops should be chosen based on these factors. TRIAL REGISTRATION NUMBER: UMIN000035155.

Real-Time Risk Score for Glaucoma Mass Screening by Spectral Domain Optical Coherence Tomography: Development and Validation.

Purpose: To develop and validate a risk score assessable in real-time using only retinal thickness-related values measured by spectral domain optical coherence tomography alone for use in population-based glaucoma mass screenings. Methods: A total of 7572 participants (aged 35-74 years) underwent spectral domain optical coherence tomography examination annually between 2016 to 2021 in a population-based setting. We selected 284 glaucoma cases and 284 controls, matched by age and sex, from 11,487 scans in 2016. We conducted multivariable logistic regression with backward stepwise selection of retinal thickness-related variables to develop the diagnostic models. The developed risk scores were applied to all participants in 2018 (9720 eyes), and we randomly selected 723 scans for validation. Additional validation using the Humphrey field analyzer was conducted on 129 eyes in 2020. We assessed the models using sensitivity, specificity, the area under the receiver operating characteristic curve and positive and negative predictive values. Results: The best-predicting model achieved an area under the receiver operating characteristic curve of 0.97 (95% confidence interval, 0.96-0.98) with a sensitivity of 0.93 and specificity of 0.91. The validation dataset showed a positive predictive value of 90.8% for high-risk scorers, corresponding to 6.2% of the population, and negative predictive value of 88.2% for low-risk scorers, corresponding to 85.2%. Sensitivity and specificity for glaucoma diagnosis were 0.85 and 0.91, when we set the risk score cut-off at 90 points out of 100. Conclusions: This risk score could be used as a valid index for glaucoma screening in a population-based setting. Translational Relevance: The score is feasible by installing a simple computer application on an existing spectral domain optical coherence tomography and will help to improve the accuracy and efficiency of glaucoma screening.

Seasonal fluctuation in intraocular pressure and its associated factors in primary open-angle glaucoma.

BACKGROUND/OBJECTIVES: To evaluate seasonal fluctuations in intraocular pressure (IOP) in primary open-angle glaucoma (POAG) and its associated factors. SUBJECTS/METHODS: POAG patients treated only with glaucoma eye drops were enroled. Winter and summer IOPs were evaluated. The Seasonal fluctuation rate of IOP was defined as follows: (mean winter IOP-mean summer IOP)/mean IOP in all seasons. Multiple linear regression analysis was used to explore factors associated with the seasonal IOP fluctuation rate including: age, gender, family history of glaucoma, type of glaucoma, number of eye drops, type of eye drops, mean deviation (MD) value, MD slope, disc haemorrhage, central corneal thickness and spherical equivalent. RESULTS: Winter IOP was higher than summer IOP in 204 POAG eyes of 204 patients, including 162 eyes with normal tension glaucoma (NTG) (13.2 ± 2.7 vs. 12.0 ± 2.3 mmHg, P < 0.001). The mean age and follow-up duration were 63.3 ± 11.4 years and 140.0 ± 66.9 months. Initial MD and MD slope were -2.1 ± 3.4 dB and -0.07 ± 0.50 dB/year, respectively. POAG was positively associated with the rate of seasonal IOP fluctuations compared to NTG (ß = 5.29, P = 0.013). Family history, and timolol and carteolol use were also factors associated with the IOP fluctuation rate (ß = -6.27, P = 0.007; ß = 4.94, P = 0.030; and ß = 4.51, P = 0.042, respectively). CONCLUSIONS: We confirmed seasonal IOP fluctuations in POAG. Type of glaucoma, family history of glaucoma, and ß-blocker use might influence IOP fluctuations.

Factors Determining the Morphology of Peripapillary Retinoschisis.

PURPOSE: We conducted cross-sectional examinations to determine the frequency of peripapillary retinoschisis (PRS) in eyes with glaucoma and suspected glaucoma and analyzed the pathogenesis of PRS by using spectral-domain optical coherence tomography (SD-OCT). PATIENTS AND METHODS: In 1516 cases involving glaucoma and suspected glaucoma, we retrospectively reviewed the disc and macular volume scans obtained by SD-OCT and categorized PRS into two groups based on whether the retinoschisis was closer to the optic nerve over the Bruch's membrane opening (BMO) (ahead group) or did not go past the BMO (behind group) and then compared the characteristics between both groups. RESULTS: The total frequency of PRS was 1.49% (20/1342 eyes) in primary open-angle glaucoma (POAG) eyes and 0.59% (10/1687 eyes) in glaucoma suspects. In the behind group, PRS was mostly detected in the inner layers of the retina (retinal nerve fiber layer: 30.9%, ganglion cell layer: 21.8%, inner plexiform layer: 7.3%). However, in the ahead group, PRS was detected in the outer layers (inner nuclear layer: 10%, outer plexiform layer: 20%, outer nuclear layer: 50%). In addition, the eyes in the ahead group had significantly greater axial lengths and significantly smaller spherical equivalent values. These two differences suggest that the pulling force of the vitreous traction may play an important role in PRS only in the behind group and that the scleral stretching force may play a role in the development of PRS in the ahead group. CONCLUSION: The frequency of PRS in patients with POAG is higher than that in patients with suspected glaucoma. Both forms of PRS are affected by posterior vitreous detachment and axial length elongation. Careful follow-up is required to assess the development of PRS in glaucoma suspects. The pathogenesis of PRS has been elucidated to some degree by classifying the morphological condition of the PRS and BMO.

Seasonal Fluctuation in Intraocular Pressure and Retinal Nerve Fiber Layer Thinning in Primary Open-Angle Glaucoma.

PURPOSE: To detect seasonal fluctuations in intraocular pressure (IOP) in healthy eyes and eyes with primary open-angle glaucoma (POAG) and to evaluate whether these seasonal fluctuations affect retinal nerve fiber layer (RNFL) thinning in eyes with POAG. DESIGN: Observational, retrospective cohort study. PARTICIPANTS: Healthy population who underwent a comprehensive health check-up and patients with POAG using only topical medications were enrolled. METHODS: Kaplan-Meier survival analysis was used to compare the cumulative incidence probabilities of RNFL thinning between different seasonal IOP fluctuation groups. A Cox proportional hazards model, with adjustments for potential confounding factors, was used to evaluate the association between seasonal fluctuations in IOP and RNFL thinning. MAIN OUTCOME MEASURES: Intraocular pressure fluctuation rate calculated from winter and summer IOPs and RNFL thinning as determined by event-based analysis with high-definition OCT. RESULTS: A total of 12 686 healthy eyes and 179 eyes of 179 POAG patients showed a significantly higher IOP in winter than in summer (healthy, 13.2 ± 3.0 mmHg vs. 12.5 ± 2.9 mmHg [P < 0.001]; POAG, 13.1 ± 2.7 mmHg vs. 11.8 ± 2.3 mmHg [P < 0.001]). In POAG patients, the mean age at initial OCT and follow-up duration were 55.1 ± 11.7 years and 98.4 ± 26.4 months, respectively. The mean deviation (MD) at first visit, MD slope, and RNFL thinning rate were -2.2 ± 3.4 dB, -0.07 ± 0.44 dB/year, and -0.44 ± 0.88 µm/year, respectively. During the study period, 85 eyes (47.5%) showed RNFL thinning progression. Kaplan-Meier analysis showed that a high seasonal IOP fluctuation rate significantly suppressed RNFL thinning (P < 0.05, log-rank test). After adjusting for confounders in the Cox analysis, the seasonal IOP fluctuation rate still showed a significantly negative association with RNFL thinning (hazard ratio, 0.98; 95% confidence interval, 0.96-0.99; P = 0.005). CONCLUSIONS: Winter IOP was higher than summer IOP in both healthy and POAG eyes. The temporary IOP decline in summer, rather than a constant IOP throughout the year, may prevent glaucoma progression.

V1 Projection Zone Signals in Human Macular Degeneration Depend on Task Despite Absence of Visual Stimulus.

Identifying the plastic and stable components of the visual cortex after retinal loss is an important topic in visual neuroscience and neuro-ophthalmology.1-5 Humans with juvenile macular degeneration (JMD) show significant blood-oxygen-level-dependent (BOLD) responses in the primary visual area (V1) lesion projection zone (LPZ),6 despite the absence of the feedforward signals from the degenerated retina. Our previous study7 reported that V1 LPZ responds to full-field visual stimuli during the one-back task (OBT), not during passive viewing, suggesting the involvement of task-related feedback signals. Aiming to clarify whether visual inputs to the intact retina are necessary for the LPZ responses, here, we measured BOLD responses to tactile and auditory stimuli for both JMD patients and control participants with and without OBT. Participants were instructed to close their eyes during the experiment for the purpose of eliminating retinal inputs. Without OBT, no V1 responses were detected in both groups of participants. With OBT, to the contrary, both stimuli caused substantial V1 responses in JMD patients, but not controls. Furthermore, we also found that the task-dependent activity in V1 LPZ became less pronounced when JMD patients opened their eyes, suggesting that task-related feedback signals can be partially suppressed by residual feedforward signals. Modality-independent V1 LPZ responses only in the task condition suggest that V1 LPZ responses reflect task-related feedback signals rather than reorganized feedforward visual inputs.

FDT Perimetry for Glaucoma Detection in Comprehensive Health Checkup Service.

We aimed to investigate the efficacy of frequency doubling technology (FDT) perimetry for glaucoma detection in comprehensive screening examinations. We performed a retrospective analysis of prospectively collected data of participants who underwent a comprehensive health checkup service. Participants with glaucoma were excluded. In the first year, 2024 participants (46.8 ± 9.4 years) who underwent FDT perimetry and fundus photography were classified as the FDT group, whereas 3052 participants (42.2 ± 8.2 years) who underwent only fundus photography were classified as the non-FDT control group. Participants with abnormal findings on FDT perimetry and/or fundus photography were recommended to undergo further complete examination. All participants reported whether they had been newly diagnosed with glaucoma within 2 years of the first visit. In the FDT group, 23 (1.14%) participants were newly diagnosed with glaucoma. Among them, 20 (87.0%) had abnormal FDT perimetry findings and 12 (52.2%) had abnormal findings on fundus photography. The positive-predictive value (PPV) of FDT perimetry was 16.5% (20/121) and that of fundus photography was 13.3% (12/90). In participants with abnormal findings on both tests, the PPV was 26.2%. In the non-FDT group, 15 (0.49%) participants were newly diagnosed with glaucoma. Among them, 9 (60.0%) had abnormal findings on fundus photography. The PPV of fundus photography was 10.8% (9/83). The glaucoma detection rate, analyzed using age adjustment, was significantly higher in the FDT group than that in the non-FDT group (0.97% versus 0.47%, P=0.041). FDT perimetry, even if performed by nonspecialized physicians, could improve glaucoma detection when used in addition to fundus photography. This study was registered with UMIN000037951.

Association between Combined Structure Function Index and Glaucoma Severity.

The aim of this study was to investigate the relationship between combined structure function index (CSFI) and standard automated perimetry (SAP) parameters such as mean deviation (MD) and visual field index (VFI) in open-angle glaucoma (OAG). We retrospectively reviewed medical records from September 2009 to July 2015, which included 195 eyes of 195 patients with OAG or normal-tension glaucoma who underwent SAP and optical coherence tomography on the same day (male: female, 128 : 67; mean age, 61.4 ± 11.3 years; mean spherical equivalent, -2.39 ± 2.3 D). We divided participants into three stages based on MD value: early, MD > -6 dB; middle, -6 dB ≥ MD ≥ -12 dB; and advanced, MD < 12 dB. We then evaluated correlations between CSFI and SAP parameters in each stage using Pearson's correlation coefficient. Mean CSFI (%), mean MD (dB), and VFI (%) in each stage were early (22.4, -2.13, and 94.0); middle (47.9, -8.78, and 75.4); and advanced (68.3, -17.32, and 49.0), respectively. Correlations between CSFI and whole, early, middle, and advanced MD were -0.88 (p < 0.001), -0.68, -0.24, and -0.76, respectively. Correlations between CSFI and whole, early, middle, and advanced VFI were -0.86 (p < 0.001), -0.59, -0.20, and -0.83, respectively. Consistency between CSFI and SAP indices in middle-stage glaucoma was low.

Diffusivity and quantitative T1 profile of human visual white matter tracts after retinal ganglion cell damage.

In patients with retinal ganglion cell diseases, recent diffusion tensor imaging (DTI) studies have revealed structural abnormalities in visual white matter tracts such as the optic tract, and optic radiation. However, the microstructural origin of these diffusivity changes is unknown as DTI metrics involve multiple biological factors and do not correlate directly with specific microstructural properties. In contrast, recent quantitative T1 (qT1) mapping methods provide tissue property measurements relatively specific to myelin volume fractions in white matter. This study aims to improve our understanding of microstructural changes in visual white matter tracts following retinal ganglion cell damage in Leber's hereditary optic neuropathy (LHON) patients by combining DTI and qT1 measurements. We collected these measurements from seven LHON patients and twenty age-matched control subjects. For all individuals, we identified the optic tract and the optic radiation using probabilistic tractography, and evaluated diffusivity and qT1 profiles along them. Both diffusivity and qT1 measurements in the optic tract differed significantly between LHON patients and controls. In the optic radiation, these changes were observed in diffusivity but were not evident in qT1 measurements. This suggests that myelin loss may not explain trans-synaptic diffusivity changes in the optic radiation as a consequence of retinal ganglion cell disease.

Age-related macular degeneration affects the optic radiation white matter projecting to locations of retinal damage.

We investigated the impact of age-related macular degeneration (AMD) on visual acuity and the visual white matter. We combined an adaptive cortical atlas and diffusion-weighted magnetic resonance imaging (dMRI) and tractography to separate optic radiation (OR) projections to different retinal eccentricities in human primary visual cortex. We exploited the known anatomical organization of the OR and clinically relevant data to segment the OR into three primary components projecting to fovea, mid- and far-periphery. We measured white matter tissue properties-fractional anisotropy, linearity, planarity, sphericity-along the aforementioned three components of the optic radiation to compare AMD patients and controls. We found differences in white matter properties specific to OR white matter fascicles projecting to primary visual cortex locations corresponding to the location of retinal damage (fovea). Additionally, we show that the magnitude of white matter properties in AMD patients' correlates with visual acuity. In sum, we demonstrate a specific relation between visual loss, anatomical location of retinal damage and white matter damage in AMD patients. Importantly, we demonstrate that these changes are so profound that can be detected using magnetic resonance imaging data with clinical resolution. The conserved mapping between retinal and white matter damage suggests that retinal neurodegeneration might be a primary cause of white matter degeneration in AMD patients. The results highlight the impact of eye disease on brain tissue, a process that may become an important target to monitor during the course of treatment.