The clinical utility of a glaucoma polygenic risk score in four population-based European-ancestry cohorts.

OBJECTIVE: We used a polygenic risk score (PRS) to identify high-risk groups for primary open-angle glaucoma (POAG) within population-based cohorts. DESIGN: Secondary analysis of four prospective population-based studies. PARTICIPANTS: We included four European-ancestry cohorts: the United States (US) based Nurses' Health Study (NHS), NHS2, and the Health Professionals Follow-up Study, and the Rotterdam Study (RS) in the Netherlands. The US cohorts included female nurses and male health professionals aged 55+ years. The RS included residents aged 45 years or older living in Rotterdam, the Netherlands. METHODS: PRS weights were estimated by applying the Lassosum method on imputed genotype and phenotype data from the UK-Biobank. This resulted in 144,020 variants, single nucleotide polymorphism (SNPs) and indels, with non-zero betas that we used to calculate a PRS in the target populations. Using multivariable Cox proportional hazard models, we estimated the relationship between the standardized PRS and relative risk for POAG. Additionally, POAG prediction was tested by calculating these models' concordance (Harrell's C-statistic). Finally, we assessed the association between PRS tertiles and glaucoma-related traits. MAIN OUTCOME MEASURES: The relative risk for POAG and Harrell's C-statistic (the equivalent of an area-under-the-curve for longitudinal models). RESULTS: Among 1,046 cases and 38,809‬ controls, the relative risk (95% confidence interval) for POAG for participants in the highest PRS quintile was 3.99 (3.08, 5.18) in the US cohorts, and 4.89 (2.93, 8.17) in the Rotterdam Study, compared with participants with median genetic risk (3rd quintile). In restricted cubic spline analyses, the relation between continuous PRS and POAG risk increased exponentially in the US and Rotterdam cohorts (Pspline<0.05). Combining age, sex, intraocular pressure >25 mmHg, and family history resulted in a meta-analyzed concordance of 0.75 (0.73, 0.75). Adding the PRS to this model improved the concordance to 0.82 (0.80, 0.84). In a meta-analysis of all cohorts, cases in the highest tertile had a larger cup-disc ratio at diagnosis, by 0.11 (0.07, 0.15), and a 2.07-fold increased risk of requiring glaucoma surgery (1.19, 3.60). CONCLUSIONS: Incorporating a PRS into a POAG predictive model improves identification concordance from 0.75 up to 0.82, supporting its potential for guiding more cost-effective screening strategies.

Long-term Alcohol Consumption and Risk of Exfoliation Glaucoma or Glaucoma Suspect Status among United States Health Professionals.

PURPOSE: To assess the association between intakes of total alcohol and individual alcoholic beverages and the incidence of exfoliation glaucoma/glaucoma suspect (XFG/XFGS) status. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 195 408 participants in the Nurses' Health Study (1980-2018), the Health Professionals Follow-up Study (1986-2018), and the Nurses' Health Study II (1991-2019) were followed biennially. Eligible participants at each 2-year risk period were ≧ 40 years and free of XFG/XFGS status with available data on diet and ophthalmic examination findings. METHODS: Cumulatively averaged total (primary exposure) and individual alcoholic beverage (beer, wine, and liquor) intakes from validated dietary information every 2-4 years. MAIN OUTCOME MEASURES: Confirmed incident XFG/XFGS status using medical records. We used per-eye Cox proportional hazards models, accounting for intereye correlations, to estimate multivariate-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs). RESULTS: During 6 877 823 eye-years of follow-up, 705 eyes with XFG/XFGS status were documented. Greater total alcohol consumption was associated significantly with higher XFG/XFGS status risk: the MVRR for XFG/XFGS status for cumulatively averaged alcohol consumption of ≧15 g/day or more versus nondrinking was 1.55 (95% CI, 1.17-2.07; P = 0.02 for trend). Long- and short-term alcohol intake was associated significantly with XFG/XFGS status risk, with the strongest associations with cumulatively averaged alcohol intake as of 4 years before diagnosis (MVRR ≥ 15 g/day vs. nondrinking, 1.65; 95% CI, 1.25-2.18; P = 0.002 for trend). Compared with nondrinkers, consuming ≧ 3.6 drinks of beer, wine, or liquor per week was associated with the following MVRRs for XFG/XFGS status: 1.26 (95% CI, 0.89-1.77; P = 0.40 for trend), 1.30 (95% CI, 1.00-1.68; P = 0.15 for trend), and 1.46 (95% CI, 1.15-1.85; P = 0.01 for trend), respectively. We did not observe interactions by age, latitude, residential tier, or intakes of folate or vitamin A (P > 0.40 for interaction); however, the association between alcohol and XFG/XFGS status was suggestively stronger for those without a family history of glaucoma (P = 0.10 for interaction). CONCLUSIONS: Long-term alcohol consumption was associated with a higher risk of XFG/XFGS status. Our findings provide further clues regarding the XFG/XFGS etiology.

Body mass index and colorectal cancer risk: A Mendelian randomization study.

Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2 ) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations.

Relation Between Body Mass Index and Dry Eye Disease: The Japan Public Health Center-Based Prospective Study for the Next Generation.

OBJECTIVE: To investigate the relation between body mass index (BMI) and dry eye disease (DED). METHODS: We conducted a cross-sectional questionnaire-based survey in 85,264 Japanese men and women aged 40 to 74 years who participated in the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). Dry eye disease was defined as the presence of severe symptoms or clinical diagnosis. A multivariable logistic regression model was used to estimate the odds ratios (ORs) of DED associated with BMI and their two-sided 95% confidence intervals (CIs). We adjusted for age, cohort area, visual display terminal time, smoking status, alcohol intake, education status, income status, as well as history of hormone replacement therapy for women. RESULTS: Prevalence of DED was 23.4% (n = 19,985; 6,289 men, 13,696 women). Higher BMI was correlated with a lower prevalence of DED in a dose-response fashion, with an adjusted OR of DED (95% CI) per 1 kg/m2 increment of BMI of 0.98 (95% CI: 0.97-0.99) for men and 0.97 (95% CI: 0.97-0.98) for women. CONCLUSIONS: This large population-based study showed an inverse relationship between BMI and prevalence of DED in a Japanese population. Underestimation of DED is warned, especially for participants with high BMI.

Long-term status of predicted body fat percentage, body mass index and other anthropometric factors with risk of colorectal carcinoma: Two large prospective cohort studies in the US.

Anthropometric measurements, such as body mass index (BMI), waist circumference, and body fat percentage, have been used as indicators of obesity. Despite evidence that excess body fat is a risk factor for colorectal carcinoma (CRC), the magnitude of the association of BMI and other obesity indicators with the long-term risk of CRC remains unclear. Utilizing a Cox proportional hazards regression model, we examined differential associations between predicted body fat percentage and BMI with the risk of CRC (n = 2,017). The associations between CRC incidence and different adiposity measurements were also assessed. Predicted body fat percentage had a similar increased risk of CRC risk as BMI. In multivariable-adjusted analyses, the hazard ratio for CRC in the second to fifth quintiles (compared to the first quintile) of predicted body fat percentage were 1.32, 1.31, 1.53 and 2.09 for men (ptrend < 0.001) and 0.91, 0.90, 0.98 and 1.15 for women (ptrend = 0.03). Among various anthropometric measurements, predicted fat mass and waist circumference were slightly more strongly associated with CRC risk than BMI. In conclusion, the novel anthropometric prediction equations provided further evidence that a greater amount of body fat might contribute to CRC risk in both sexes. An innovative approach enabled us to estimate the susceptibilities of specific body composition with CRC risk, in an inexpensive and minimally invasive manner. Furthermore, the typically used measures of BMI and waist circumference are robust measures of adiposity to predict cancer risk in a relatively healthy population.

Dietary glycemic and insulin scores and colorectal cancer survival by tumor molecular biomarkers.

Accumulating evidence suggests that post-diagnostic insulin levels may influence colorectal cancer (CRC) survival. Yet, no previous study has examined CRC survival in relation to a post-diagnostic diet rich in foods that increase post-prandial insulin levels. We hypothesized that glycemic and insulin scores (index or load; derived from food frequency questionnaire data) may be associated with survival from specific CRC subtypes sensitive to the insulin signaling pathway. We prospectively followed 1,160 CRC patients from the Nurses' Health Study (1980-2012) and Health Professionals Follow-Up Study (1986-2012), resulting in 266 CRC deaths in 10,235 person-years. CRC subtypes were defined by seven tumor biomarkers (KRAS, BRAF, PIK3CA mutations, and IRS1, IRS2, FASN and CTNNB1 expression) implicated in the insulin signaling pathway. For overall CRC and each subtype, hazard ratio (HR) and 95% confidence interval (95% CI) for an increase of one standard deviation in each of glycemic and insulin scores were estimated using time-dependent Cox proportional hazards model. We found that insulin scores, but not glycemic scores, were positively associated with CRC mortality (HR = 1.19, 95% CI = 1.02-1.38 for index; HR = 1.23, 95% CI = 1.04-1.47 for load). The significant positive associations appeared more pronounced among PIK3CA wild-type cases and FASN-negative cases, with HR ranging from 1.36 to 1.60 across insulin scores. However, we did not observe statistically significant interactions of insulin scores with PIK3CA, FASN, or any other tumor marker (p interaction > 0.12). While additional studies are needed for definitive evidence, a high-insulinogenic diet after CRC diagnosis may contribute to worse CRC survival.

Body mass index and risk of colorectal carcinoma subtypes classified by tumor differentiation status.

Previous studies suggest that abnormal energy balance status may dysregulate intestinal epithelial homeostasis and promote colorectal carcinogenesis, yet little is known about how host energy balance and obesity influence enterocyte differentiation during carcinogenesis. We hypothesized that the association between high body mass index (BMI) and colorectal carcinoma incidence might differ according to tumor histopathologic differentiation status. Using databases of the Nurses' Health Study and Health Professionals Follow-up Study, and duplication-method Cox proportional hazards models, we prospectively examined an association between BMI and the incidence of colorectal carcinoma subtypes classified by differentiation features. 120,813 participants were followed for 26 or 32 years and 1528 rectal and colon cancer cases with available tumor pathological data were documented. The association between BMI and colorectal cancer risk significantly differed depending on the presence or absence of poorly-differentiated foci (Pheterogeneity = 0.006). Higher BMI was associated with a higher risk of colorectal carcinoma without poorly-differentiated foci (≥30.0 vs. 18.5-22.4 kg/m2: multivariable-adjusted hazard ratio, 1.87; 95% confidence interval, 1.49-2.34; Ptrend < 0.001), but not with risk of carcinoma with poorly-differentiated foci (Ptrend = 0.56). This differential association appeared to be consistent in strata of tumor microsatellite instability or FASN expression status, although the statistical power was limited. The association between BMI and colorectal carcinoma risk did not significantly differ by overall tumor differentiation, mucinous differentiation, or signet ring cell component (Pheterogeneity > 0.03, with the adjusted α of 0.01). High BMI was associated with risk of colorectal cancer subtype containing no poorly-differentiated focus. Our findings suggest that carcinogenic influence of excess energy balance might be stronger for tumors that retain better intestinal differentiation throughout the tumor areas.

Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltrate.

Higher body mass index (BMI), higher body adiposity and obesity have been associated with increased risk of colorectal cancer. Evidence suggests that excess energy balance may influence systemic immune and inflammatory status. Thus, we hypothesized that the positive association between BMI and colorectal cancer risk might differ according to colorectal carcinoma subtypes according to levels of histopathological lymphocytic reaction to tumor. We collected biennial questionnaire data on weight and baseline height information in two prospective cohort studies, the Nurses' Health Study (1980-2010) and the Health Professionals Follow-up Study (1986-2010). Utilizing duplication-method Cox proportional hazards regression models, we prospectively assessed the association between BMI and risk of colorectal cancer subtypes according to the degree of Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, the overall lymphocytic reaction score, or T-cell [CD3(+) , CD8(+) , CD45RO (PTPRC)(+) or FOXP3(+) ] density in tumor tissue. Statistical significance level was adjusted for multiple hypotheses testing by Bonferroni correction. During follow up of 1,708,029 men and women (over 3,346,752 person-years), we documented 1,436 incident rectal and colon cancer cases with available formalin-fixed paraffin-embedded tumor tissue materials and pathological immunity data. BMI was significantly associated with higher risk of overall colorectal cancer (Ptrend < 0.001); however, the association of BMI with colorectal carcinoma risk did not significantly differ by the level of lymphocytic reaction or T-cell infiltration in tumor tissue status (Pheterogeneity > 0.10). BMI may be associated with risk of colorectal cancer regardless of levels of lymphocytic response to tumor.

Survival Benefit of Exercise Differs by Tumor IRS1 Expression Status in Colorectal Cancer.

BACKGROUND: High-level physical activity is associated with lower colorectal cancer (CRC) mortality, likely through insulin sensitization. Insulin receptor substrate 1 (IRS1) is a mediator of insulin and insulin-like growth factor (IGF) signaling pathways, and its down-regulation is associated with insulin resistance. Therefore, we hypothesized that tumor IRS1 expression status might modify cellular sensitivity to insulin and IGF, and the prognostic association of physical activity. METHODS: We assessed IRS1 expression level in 371 stage I-III rectal and colon cancers in the Nurses' Health Study and the Health Professionals Follow-up Study by immunohistochemistry. In survival analysis, Cox proportional hazards model was used to assess an interaction between post-diagnosis physical activity (ordinal scale of sex-specific quartiles Q1 to Q4) and IRS1 expression (ordinal scale of negative, low, and high), controlling for potential confounders, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 (LINE-1) methylation level, and KRAS, BRAF, and PIK3CA mutation status. RESULTS: There was a statistically significant interaction between post-diagnosis physical activity and tumor IRS1 expression in CRC-specific mortality analysis (P interaction = 0.005). Multivariable hazard ratio (95% confidence interval) for higher post-diagnosis physical activity (Q3-Q4 vs. Q1-Q2) was 0.15 (0.02-1.38) in the IRS1-negative group, 0.45 (0.19-1.03) in the IRS1-low group, and 1.32 (0.50-3.53) in the IRS1-high group. CONCLUSIONS: The association of post-diagnosis physical activity with colorectal carcinoma patient survival may differ by tumor IRS1 expression level. If validated, tumor IRS1 expression status may serve as a predictive marker to identify subgroups of patients who might gain greater survival benefit from an increased level of exercise.

Symptomatic Presbyopia may Develop Earlier in Patients With Glaucoma-A Cross-Sectional Retrospective Cohort Study.

Purpose: The purpose of this study was to explore risk factors for symptomatic presbyopia, defined as near add power ≥1.50 diopters, in patients with glaucoma. Methods: Treated glaucoma (n = 56), untreated glaucoma (n = 21), and control individuals (n = 376), aged 40 to 55 years at first visit, were enrolled in the study, and near add power, retinal thickness, and visual field were examined. The association between near add power and ocular parameters and the odds ratios (ORs) for symptomatic presbyopia were investigated. Survival analysis for symptomatic presbyopia was conducted. Results: Age, astigmatic power, mean deviation, and ganglion cell complex thickness were associated with near add power. The OR for symptomatic presbyopia was significant for age (OR = 1.51), astigmatism (OR = 1.01), mean deviation (OR = 0.72), ganglion cell complex thickness (OR = 0.98), treated and untreated glaucoma (OR = 2.09), and use of glaucoma eye drops (OR = 3.33). Survival analysis showed that the treated glaucoma group reached the near add power endpoint of ≥1.50 D (symptomatic presbyopia) significantly earlier than the other two groups, and there was no difference between the control and untreated glaucoma groups. Conclusions: Glaucoma patients treated with eye drops may start near correction earlier. Translational Relevance: Symptomatic presbyopia may develop earlier in patients with glaucoma, and our findings could further contribute to better management and understanding of presbyopia with glaucoma.

Presbyopia, Dry Eye, and Retinal Thickness in the Middle-Aged Population: Focusing on Sex Differences.

Purpose: Risk factors for presbyopia have not been fully determined although previous studies suggested presbyopia was associate with age, dry eye, and retinal ganglion cell complex thickness (GCC). We accessed these signs and common ocular symptoms in the middle-aged population focusing on sex differences when women have drastic hormonal change. Methods: This cohort study consecutively enrolled 2743 patients aged 36-45 years (n=1000), 46-55 years (n=1000), and 56-65 years (n=743). All underwent ocular surface tests and had near add power and GCC measured. Common ocular symptoms were asked using questionnaire. Results: Among female participants, visual symptoms (eye strain and photophobia) were more prevalent in the age group 46-55, whereas non-visual symptoms (dryness, irritation, and pain) were not. We identified symptomatic presbyopia (near add power ≥ 1.5D) in 14.4%, 73.8%, and 97.8%, positive corneal staining in 29.1%, 23.8%, and 23.9%, and a mean GCC of 98.2 µm, 105.3 µm, and 89.6 µm in the age groups 36-45, 46-55, and 56-65, respectively. Mean tear break-up time were 3.3, 3.5, and 3.3 seconds, respectively. Results indicated a large progression of presbyopia (P<0.01) from the period of 36-45 years onward and significantly increased GCC (P<0.01) in women of age group 46-55. No notable tendency was observed in symptoms and GCC for male participants. Conclusion: Visual symptoms in women were worse between 46 and 55 years than before or after these ages. The increase of symptomatic presbyopia and GCC may be contributing to visual symptoms in addition to menopausal transition symptoms in this age group.

Establishing the cutoff value of near visual acuity for assessment of early presbyopia.

PURPOSE: There is limited evidence to evaluate the numerical cutoff point for detecting early presbyopia. Thus, we aimed to establish a clinically relevant optimal cutoff value of near visual acuity for detecting early presbyopia. STUDY DESIGN: Prospective diagnostic accuracy study. METHODS: We included consecutive individuals aged ≥ 20 years with a binocular-corrected distance visual acuity of ≥ 20/25 who did not undergo ophthalmic surgery between December 17, 2020 and December 19, 2021, at two healthcare facilities in Japan. Binocular distance-corrected near visual acuity at 40 cm, accommodative amplitude, awareness of presbyopia, and Near Activity Visual Questionnaire scores were examined. The optimal cutoff values of distance-corrected near visual acuity for diagnosing early presbyopia were evaluated using receiver operating characteristic plots. RESULTS: Among 115 participants, 74 (64.3%) had presbyopia. The proportion of participants with no difficulty performing near-vision tasks decreased markedly when near visual acuity decreased to 20/20 (> 0.00 logMAR). A cutoff value of 0.00 logMAR for distance-corrected near visual acuity was optimal, showing high sensitivity of 56.76% and specificity of 92.68%, as opposed to the commonly used cutoff value of 0.40 logMAR (20/50; sensitivity, 9.46% and specificity, 100%) for diagnosing early presbyopia. CONCLUSION: Near visual acuity of 0.00 logMAR (20/20) could be the optimal cutoff value for diagnosing early presbyopia.

Slowing of Greater Axial Length Elongation Stemming from the Coronavirus Disease 2019 Pandemic with Increasing Time Outdoors: The Tokyo Myopia Study.

Purpose: To investigate the changes in axial length (AL) elongation and other ocular parameters before and during the coronavirus disease 2019 pandemic. Design: A longitudinal school-based study. Participants: Public elementary schoolchildren in Tokyo (grades 1-6; age, 6-12 years) participated in this study from 2018 to 2021. Methods: All participants underwent eye examinations and provided written consent to measurements of the noncycloplegic refraction and ocular biometry including AL, among others. The students' parents also completed a questionnaire about the students' lifestyles. We included the right eye in our analysis and compared the changes in the ocular parameters among the periods using a linear mixed-effects model for repeated measures and examined the univariate and step-wise multiple regression analyses to evaluate the associations between myopia and other covariates. Main Outcome Measures: Changes in AL elongation and other ocular parameters from 2018 to 2019 (prepandemic), that of 2019 to 2020 (immediately after the pandemic onset), and that of 2020 to 2021 (during the pandemic). Results: A total of 578 students before the pandemic period, 432 immediately after the pandemic onset, and 457 during the pandemic period were evaluated. The changes in the ALs and spherical equivalents (SEs) a year before, immediately after onset, and during the pandemic were 0.31 mm/-0.20 diopter, 0.38 mm/-0.27 diopter, and 0.28 mm/-0.47 diopter, respectively (ALs, P < 0.001; SEs, P = 0.014). The results of the questionnaire showed that time spent outdoors daily had changed during the 3 years to 79, 63, and 77 minutes/day, respectively (P < 0.001). Time spent using smartphones or tablets increased year by year to 41, 52, and 62 minutes/day (P < 0.001). The greatest AL elongation occurred during the period when the shortest amount of time was spent outdoors during the 3 years. Conclusions: These results suggested that the school closures and decreasing time spent outdoors might have caused greater AL elongation among schoolchildren in Tokyo; however, it is possible that, although the time spent in near work still increased, the return to the time spent outdoors to the prepandemic levels may have affected the slowing of AL elongation after lockdown. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Relation between a history of glaucoma and subjective happiness: the JPHC-Next study.

OBJECTIVE: This population-based, cross-sectional study was performed to investigate the relationship between a history of glaucoma and subjective happiness. METHODS AND ANALYSIS: We conducted a cross-sectional questionnaire-based survey of 92 397 Japanese men and women aged 40-74 who participated in the Japan Public Health Center-based Prospective Study for the Next Generation study. A multivariable logistic regression model was used to estimate the ORs of glaucoma associated with subjective happiness and their two-sided 95% CIs. RESULTS: Among 40 727 men and 51 670 women, 1733 participants (635 men, 1098 women) had a history of glaucoma. The odds of unhappiness in male participants with a history of glaucoma were higher (OR 1.26; 95% CI 1.05 to 1.51) than in female participants (OR 1.05; 95% CI 0.90 to 1.23). In a subgroup analysis stratified by age, among participants with a history of glaucoma, males in the younger group (40-59 years) showed the most robust association with unhappiness (OR 1.40; 95% CI 1.04 to 1.88). CONCLUSIONS: These findings suggest that a history of glaucoma is related with subjective unhappiness, especially in men.

AI-based diagnosis of nuclear cataract from slit-lamp videos.

In ophthalmology, the availability of many fundus photographs and optical coherence tomography images has spurred consideration of using artificial intelligence (AI) for diagnosing retinal and optic nerve disorders. However, AI application for diagnosing anterior segment eye conditions remains unfeasible due to limited standardized images and analysis models. We addressed this limitation by augmenting the quantity of standardized optical images using a video-recordable slit-lamp device. We then investigated whether our proposed machine learning (ML) AI algorithm could accurately diagnose cataracts from videos recorded with this device. We collected 206,574 cataract frames from 1812 cataract eye videos. Ophthalmologists graded the nuclear cataracts (NUCs) using the cataract grading scale of the World Health Organization. These gradings were used to train and validate an ML algorithm. A validation dataset was used to compare the NUC diagnosis and grading of AI and ophthalmologists. The results of individual cataract gradings were: NUC 0: area under the curve (AUC) = 0.967; NUC 1: AUC = 0.928; NUC 2: AUC = 0.923; and NUC 3: AUC = 0.949. Our ML-based cataract diagnostic model achieved performance comparable to a conventional device, presenting a promising and accurate auto diagnostic AI tool.

Associations between fatty acid intake and diabetic retinopathy in a Japanese population.

Residents of Chikusei City, aged 40-74 years, underwent systemic and ophthalmological screening, and participants with diabetes were included in this analysis. Dietary intake was assessed using a food frequency questionnaire and calculated as a percentage of the total energy. The presence of diabetic retinopathy (DR) was defined as Early Treatment Diabetic Retinopathy Study levels ≥ 20 in either eye. The association between dietary fatty acid intake and DR has been examined in a cross-sectional study. Among the 647 diabetic participants, 100 had DR. The mean total fat and saturated fatty acid (SFA) intakes were 22.0% and 7.3% of the total energy intake, respectively. After adjusting for potential confounders, the highest quartiles of total fat and SFA intake were positively associated with the presence of DR compared with the lowest quartiles (odds ratios (95% confidence intervals), 2.61 (1.07-6.39), p for trend = 0.025, and 2.40 (1.12-5.17), p for trend = 0.013, respectively). No significant associations were found between DR prevalence and monounsaturated or unsaturated fatty acid intake. These results suggest that a high intake of fat and SFA may affect the development of DR, even in individuals whose total fat intake is generally much lower than that of Westerners.

Association Between Fatty Acid Intakes and Age-Related Macular Degeneration in a Japanese Population: JPHC-NEXT Eye Study.

Purpose: To determine the associations between fatty acid intakes and the prevalence of age-related macular degeneration (AMD) under a population-based cross-sectional study. Methods: Residents of Chikusei City aged ≥40 years underwent systemic and eye screening. AMD was graded according to a modified version of the Age-Related Eye Disease Study classification. Dietary intake was assessed using a food frequency questionnaire and was adjusted for total energy intake. Results: Altogether, 10,788 eyes of 5394 participants, 2116 men (mean [standard deviation (SD)] age, 62.4 [9.4] years) and 3278 women (60.6 [9.5] years), were included. The mean daily total fat intakes were 52.8 g and 59.0 g in men and women, respectively. After adjustments for potential confounders, saturated fatty acid (SFA) intake was inversely associated with the prevalence of any AMD in men (for each energy-adjusted 1-SD increase: odds ratio [OR], 0.86; 95% confidence interval [CI], 0.74-1.00). Significant trends were found for decreasing odds ratios of AMD with increasing SFA, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA) intake (P for trend = 0.02, 0.04, and 0.04, respectively). In women, only a significant association was observed between the second quartile of linolenic acid intake and the prevalence of any AMD (OR, 0.78; 95% CI, 0.62-0.99). Conclusions: We found an inverse association of SFA intake and a weak inverse association of MUFA and PUFA intakes with the prevalence of any AMD in a Japanese population. Translational Relevance: Adequate fatty acid intake may be necessary to prevent or decelerate AMD.

Artificial intelligence to estimate the tear film breakup time and diagnose dry eye disease.

The use of artificial intelligence (AI) in the diagnosis of dry eye disease (DED) remains limited due to the lack of standardized image formats and analysis models. To overcome these issues, we used the Smart Eye Camera (SEC), a video-recordable slit-lamp device, and collected videos of the anterior segment of the eye. This study aimed to evaluate the accuracy of the AI algorithm in estimating the tear film breakup time and apply this model for the diagnosis of DED according to the Asia Dry Eye Society (ADES) DED diagnostic criteria. Using the retrospectively corrected DED videos of 158 eyes from 79 patients, 22,172 frames were annotated by the DED specialist to label whether or not the frame had breakup. The AI algorithm was developed using the training dataset and machine learning. The DED criteria of the ADES was used to determine the diagnostic performance. The accuracy of tear film breakup time estimation was 0.789 (95% confidence interval (CI) 0.769-0.809), and the area under the receiver operating characteristic curve of this AI model was 0.877 (95% CI 0.861-0.893). The sensitivity and specificity of this AI model for the diagnosis of DED was 0.778 (95% CI 0.572-0.912) and 0.857 (95% CI 0.564-0.866), respectively. We successfully developed a novel AI-based diagnostic model for DED. Our diagnostic model has the potential to enable ophthalmology examination outside hospitals and clinics.

Association of 25-hydroxyvitamin D with risk of overall and colorectal cancer among Japanese using a Mendelian randomization approach.

The association between vitamin D and total and colorectal cancer risk was inconsistent in observational studies. We conducted Mendelian randomization approach in which the effect of confounding might be reduced. 110 single nucleotide polymorphisms (SNPs) associated with 25-hydroxyvitamin D concentrations were systematically selected according to the "GWAS Catalog" from all ethnic populations. For the SNP-vitamin D concentration association, 3978 individuals from two Japanese cohorts were included. Regarding SNP-total and colorectal cancer association, 4543 cancer cases and 14,224 controls and 7936 colorectal cancer cases and 38,042 controls, respectively were included from the Japanese Consortium of Genetic Epidemiology and other studies in Japan. There was no significant association between the genetically predicted plasma 25-hydroxyvitamin D concentration and total or colorectal cancer in any of the MR analyses. Odds ratios per doubling in vitamin D concentration were 0.83 (95% confidence interval [CI] 0.63-1.09) for total cancer and 1.00 (95% CI 0.80-1.24) for colorectal cancer in inverse variance weighted method, 0.83 (95% CI 0.57-1.19) for total cancer and 1.01 (95% CI 0.75-1.37) for colorectal cancer in MR-Egger method. Consistent with previous MR analyses among European ancestries, there was no significant association identified between 25-hydroxyvitamin D levels and total or colorectal cancer among Asians.

Association Between Glycemic Traits and Primary Open-Angle Glaucoma: A Mendelian Randomization Study in the Japanese Population.

PURPOSE: A meta-analysis suggests a relationship between abnormal glucose metabolism and primary open-angle glaucoma (POAG); however, the causal association between them remains controversial. We therefore conducted a Mendelian randomization (MR) study to assess the causal association between genetically predicted glycemic traits and the risk of POAG. DESIGN: Two-sample MR design. METHODS: We examined the genetically predicted measures of fasting glucose, hemoglobin A1c (HbA1c), and fasting C-peptide, in relation to POAG. For the single nucleotide polymorphism (SNP)-exposure analyses, we meta-analyzed the study-level genome-wide associations of fasting glucose levels (n = 17,289; n of SNPs = 34), HbA1c (n = 52,802; n of SNPs = 43), and fasting C-peptide levels (n=1666; n of SNPs = 17) from the Japanese Consortium of Genetic Epidemiology studies. We used summary statistics from the BioBank Japan projects (n = 3980 POAG cases and 18,815 controls) for the SNP-outcome association. RESULTS: We observed no association of genetically predicted HbA1c and fasting C-peptide with POAG. The MR inverse-variance-weighted (IVW) odds ratios (ORs) were 1.44 (95% confidence interval [CI], 0.78-2.65; P = .25) for HbA1c (per 1% increment) and 0.92 (95% CI, 0.56-1.53; P = .76) for fasting C-peptide (per 2-fold increment). A significant association between fasting glucose (per 10 mg/dL-increment) and POAG was observed according to the MR IVW analysis (OR = 1.48 [95% CI, 1.10-1.79, P = .009]); however, sensitivity analyses, including MR-Egger and weighted-median methods, did not support this association (P > .10). CONCLUSIONS: We did not observe strong evidence to support the association between genetically predicted glycemic traits and POAG in the Japanese population.