Consumption of Coffee and Tea Is Associated with Macular Retinal Nerve Fiber Layer Thickness: Results from the UK Biobank.

Coffee and tea drinking are thought to be protective for the development and progression of neurodegenerative disorders. This study aims to investigate associations between coffee and tea consumption with macular retinal nerve fiber layer (mRNFL) thickness, a marker of neurodegeneration. After quality control and eligibility screening, 35,557 out of 67,321 United Kingdom (UK) Biobank participants from six assessment centers were included in this cross-sectional study. In the touchscreen questionnaire, participants were asked how many cups of coffee and tea were consumed daily on average over the last year. Self-reported coffee and tea consumption were divided into four categories including 0 cup/day, 0.5-1 cups/day, 2-3 cups/day, and ≥4 cups/day, respectively. The mRNFL thickness was measured by the optical coherence tomography (Topcon 3D OCT-1000 Mark II) and automatically analyzed by segmentation algorithms. After adjusting for covariates, coffee consumption was significantly associated with an increased mRNFL thickness (ß = 0.13, 95% CI = 0.01~0.25), which was more prominent in those who drank 2~3 cups coffee per day (ß = 0.16, 95% CI = 0.03~0.30). The mRNFL thickness was also significantly increased in tea drinkers (ß = 0.13, 95% CI = 0.01~0.26), especially for those who drank more than 4 cups of tea per day (ß = 0.15, 95% CI = 0.01~0.29). The positive associations with mRNFL thickness, indicating that both coffee and tea consumptions had likely neuroprotective potentials. Causal links and underlying mechanisms for these associations should be explored further.

A Deep Learning-Based Fully Automated Program for Choroidal Structure Analysis Within the Region of Interest in Myopic Children.

Purpose: To develop and validate a fully automated program for choroidal structure analysis within a 1500-µm-wide region of interest centered on the fovea (deep learning-based choroidal structure assessment program [DCAP]). Methods: A total of 2162 fovea-centered radial swept-source optical coherence tomography (SS-OCT) B-scans from 162 myopic children with cycloplegic spherical equivalent refraction ranging from -1.00 to -5.00 diopters were collected to develop the DCAP. Medical Transformer network and Small Attention U-Net were used to automatically segment the choroid boundaries and the nulla (the deepest point within the fovea). Automatic denoising based on choroidal vessel luminance and binarization were applied to isolate choroidal luminal/stromal areas. To further compare the DCAP with the traditional handcrafted method, the luminal/stromal areas and choroidal vascularity index (CVI) values for 20 OCT images were measured by three graders and the DCAP separately. Intraclass correlation coefficients (ICCs) and limits of agreement were used for agreement analysis. Results: The mean ± SD pixel-wise distances from the predicted choroidal inner, outer boundary, and nulla to the ground truth were 1.40 ± 1.23, 5.40 ± 2.24, and 1.92 ± 1.13 pixels, respectively. The mean times required for choroidal structure analysis were 1.00, 438.00 ± 75.88, 393.25 ± 78.77, and 410.10 ± 56.03 seconds per image for the DCAP and three graders, respectively. Agreement between the automatic and manual area measurements was excellent (ICCs > 0.900) but poor for the CVI (0.627; 95% confidence interval, 0.279-0.832). Additionally, the DCAP demonstrated better intersession repeatability. Conclusions: The DCAP is faster than manual methods. Also, it was able to reduce the intra-/intergrader and intersession variations to a small extent. Translational Relevance: The DCAP could aid in choroidal structure assessment.

The Association of Retinal age gap with metabolic syndrome and inflammation.

BACKGROUND: Metabolic syndrome (MetS) is a clustering of cardiometabolic components, posing tremendous burdens in the aging society. Retinal age gap has been proposed as a robust biomarker associated with mortality and Parkinson's disease. Although MetS and chronic inflammation could accelerate the aging process and increase the risk of mortality, the association of the retinal age gap with MetS and inflammation has not been examined yet. METHODS: Retinal age gap (retina-predicted age minus chronological age) was calculated using a deep learning model. MetS was defined as the presence of three or more of the following: central obesity, hypertension, dyslipidemia, hypertriglyceridemia, and hyperglycemia. Inflammation index was defined as a high-sensitivity C-reactive protein level above 3.0 mg/L. Logistic regression models were used to examine the associations of retinal age gaps with MetS and inflammation. RESULTS: We found that retinal age gap was significantly associated with MetS and inflammation. Specifically, compared to participants with retinal age gaps in the lowest quartile, the risk of MetS was significantly increased by 10% and 14% for participants with retinal age gaps in the third and fourth quartile (odds ratio [OR]:1.10; 95% confidence interval [CI], 1.01,1.21;, p = .030; OR: 1.14, 95% CI, 1.03,1.26; p = .012, respectively). Similar trends were identified for the risk of inflammation and combined MetS and inflammation. CONCLUSION: We found that retinal age gaps were significantly associated with MetS as well as inflammation. Given the noninvasive and cost-effective nature and the efficacy of the retinal age gap, it has great potential to be used as a screening tool for MetS in large populations.

Using deep leaning models to detect ophthalmic diseases: A comparative study.

Purpose: The aim of this study was to prospectively quantify the level of agreement among the deep learning system, non-physician graders, and general ophthalmologists with different levels of clinical experience in detecting referable diabetic retinopathy, age-related macular degeneration, and glaucomatous optic neuropathy. Methods: Deep learning systems for diabetic retinopathy, age-related macular degeneration, and glaucomatous optic neuropathy classification, with accuracy proven through internal and external validation, were established using 210,473 fundus photographs. Five trained non-physician graders and 47 general ophthalmologists from China were chosen randomly and included in the analysis. A test set of 300 fundus photographs were randomly identified from an independent dataset of 42,388 gradable images. The grading outcomes of five retinal and five glaucoma specialists were used as the reference standard that was considered achieved when ≥50% of gradings were consistent among the included specialists. The area under receiver operator characteristic curve of different groups in relation to the reference standard was used to compare agreement for referable diabetic retinopathy, age-related macular degeneration, and glaucomatous optic neuropathy. Results: The test set included 45 images (15.0%) with referable diabetic retinopathy, 46 (15.3%) with age-related macular degeneration, 46 (15.3%) with glaucomatous optic neuropathy, and 163 (55.4%) without these diseases. The area under receiver operator characteristic curve for non-physician graders, ophthalmologists with 3-5 years of clinical practice, ophthalmologists with 5-10 years of clinical practice, ophthalmologists with >10 years of clinical practice, and the deep learning system for referable diabetic retinopathy were 0.984, 0.964, 0.965, 0.954, and 0.990 (p = 0.415), respectively. The results for referable age-related macular degeneration were 0.912, 0.933, 0.946, 0.958, and 0.945, respectively, (p = 0.145), and 0.675, 0.862, 0.894, 0.976, and 0.994 for referable glaucomatous optic neuropathy, respectively (p < 0.001). Conclusion: The findings of this study suggest that the accuracy of this deep learning system is comparable to that of trained non-physician graders and general ophthalmologists for referable diabetic retinopathy and age-related macular degeneration, but the deep learning system performance is better than that of trained non-physician graders for the detection of referable glaucomatous optic neuropathy.

Association between cardiovascular health metrics and retinal ageing.

The study aims to investigate associations between cardiovascular health (CVH) metrics and retinal ageing indexed by retinal age gap. A total of 26,354 participants from the UK Biobank study with available CVH metrics and qualified retinal imaging were included in the present analysis. CVH included 7 metrics (smoking, physical activity, diet, body mass index [BMI], total cholesterol, blood pressure [BP], blood glucose). These were summarized to classify the overall CVH as poor (0-7), intermediate (8-10) or ideal (11-14). Retinal age gap was defined as the difference between biological age predicted by fundus images and chronological age. Accelerated and non-accelerated retinal ageing was defined if retinal age gap was in the upper or lower 50% quantiles of the study population, respectively. Linear and logistic regression models estimated the association of overall CVH and each metric of CVH with retinal age gap respectively. Our results showed that in the fully adjusted model, each one-unit score increase in overall CVH was negatively associated with retinal age gap (odds ratio [OR] = 0.89, 95% confidence interval [CI]: 0.87-0.92, P < 0.001). Compared with poor overall CVH, people with intermediate and ideal overall CVH had significantly lower retinal age gap (OR = 0.76, 95%CI: 0.67-0.85, P < 0.001; OR = 0.58, 95%CI: 0.50-0.67, P < 0.001). Similar associations were found between overall CVH and accelerated retinal ageing. CVH metrics including smoking, BMI, BP, and blood glucose were also significantly associated with higher retinal age gap. Taken together, we found a significant and inverse dose-response association between CVH metrics and retinal age gap, indicating that maintaining healthy metrics especially smoking, BMI, BP, and blood glucose may be crucial to slow down biological ageing.

A medication-wide association study to identify medications associated with incident clinically significant diabetic retinopathy.

Background: Diabetic retinopathy, a common microvascular complication of diabetes mellitus, is one of the leading causes of vision loss worldwide. Although some oral drugs have been suggested to affect the risk of diabetic retinopathy, systematic evaluation about the associations between medications and diabetic retinopathy is still absent. Objective: To comprehensively investigate associations of systemic medications with incident clinically significant diabetic retinopathy (CSDR). Design: Population-based cohort study. Methods: From 2006 to 2009, more than 26 000 participants residing in New South Wales were enrolled in the 45 and Up study. Diabetic participants with self-reported physician diagnosis or records of anti-diabetic medication prescriptions were finally included in the current analysis. CSDR was defined as diabetic retinopathy cases requiring retinal photocoagulation recorded in the Medicare Benefits Schedule database from 2006 to 2016. Prescriptions of systemic medication from 5 years to 30 days prior to CSDR were retrieved from the Pharmaceutical Benefits Scheme. The study participants were equally split into training and testing datasets. Logistic regression analyses were performed for the association between each of systemic medication and CSDR in the training dataset. After controlling the false discovery rate (FDR), significant associations were further validated in the testing dataset. Results: The 10-year incidence of CSDR was 3.9% (n = 404). A total of 26 systemic medications were found to be positively associated with CSDR, among which 15 were validated by the testing dataset. Additional adjustments for pertinent comorbidities suggested that isosorbide mononitrate (ISMN) (OR: 1.87, 95%CI: 1.00-3.48), calcitriol (OR: 4.08, 95% CI: 2.02-8.24), three insulins and analogues (e.g., intermediate-acting human insulin, OR: 4.28, 95% CI: 1.69-10.8), five anti-hypertensive medications (e.g., furosemide, OR: 2.53, 95% CI: 1.77-3.61), fenofibrate (OR: 1.96, 95% CI: 1.36-2.82) and clopidogrel (OR: 1.72, 95% CI: 1.15-2.58) were independently associated with CSDR. Conclusion: This study investigated the association of a full spectrum of systemic medications with incident CSDR. ISMN, calcitriol, clopidogrel, a few subtypes of insulin, anti-hypertensive and cholesterol-lowering medications were found to be associated with incident CSDR.

Integrating oculomics with genomics reveals imaging biomarkers for preventive and personalized prediction of arterial aneurysms.

Objective: Arterial aneurysms are life-threatening but usually asymptomatic before requiring hospitalization. Oculomics of retinal vascular features (RVFs) extracted from retinal fundus images can reflect systemic vascular properties and therefore were hypothesized to provide valuable information on detecting the risk of aneurysms. By integrating oculomics with genomics, this study aimed to (i) identify predictive RVFs as imaging biomarkers for aneurysms and (ii) evaluate the value of these RVFs in supporting early detection of aneurysms in the context of predictive, preventive and personalized medicine (PPPM). Methods: This study involved 51,597 UK Biobank participants who had retinal images available to extract oculomics of RVFs. Phenome-wide association analyses (PheWASs) were conducted to identify RVFs associated with the genetic risks of the main types of aneurysms, including abdominal aortic aneurysm (AAA), thoracic aneurysm (TAA), intracranial aneurysm (ICA) and Marfan syndrome (MFS). An aneurysm-RVF model was then developed to predict future aneurysms. The performance of the model was assessed in both derivation and validation cohorts and was compared with other models employing clinical risk factors. An RVF risk score was derived from our aneurysm-RVF model to identify patients with an increased risk of aneurysms. Results: PheWAS identified a total of 32 RVFs that were significantly associated with the genetic risks of aneurysms. Of these, the number of vessels in the optic disc ('ntreeA') was associated with both AAA (ß = -0.36, P = 6.75e-10) and ICA (ß = -0.11, P = 5.51e-06). In addition, the mean angles between each artery branch ('curveangle_mean_a') were commonly associated with 4 MFS genes (FBN1: ß = -0.10, P = 1.63e-12; COL16A1: ß = -0.07, P = 3.14e-09; LOC105373592: ß = -0.06, P = 1.89e-05; C8orf81/LOC441376: ß = 0.07, P = 1.02e-05). The developed aneurysm-RVF model showed good discrimination ability in predicting the risks of aneurysms. In the derivation cohort, the C-index of the aneurysm-RVF model was 0.809 [95% CI: 0.780-0.838], which was similar to the clinical risk model (0.806 [0.778-0.834]) but higher than the baseline model (0.739 [0.733-0.746]). Similar performance was observed in the validation cohort, with a C-index of 0.798 (0.727-0.869) for the aneurysm-RVF model, 0.795 (0.718-0.871) for the clinical risk model and 0.719 (0.620-0.816) for the baseline model. An aneurysm risk score was derived from the aneurysm-RVF model for each study participant. The individuals in the upper tertile of the aneurysm risk score had a significantly higher risk of aneurysm compared to those in the lower tertile (hazard ratio = 17.8 [6.5-48.8], P = 1.02e-05). Conclusion: We identified a significant association between certain RVFs and the risk of aneurysms and revealed the impressive capability of using RVFs to predict the future risk of aneurysms by a PPPM approach. Our finds have great potential to support not only the predictive diagnosis of aneurysms but also a preventive and more personalized screening plan which may benefit both patients and the healthcare system. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00315-7.

Axial Shortening in Myopic Children after Repeated Low-Level Red-Light Therapy: Post Hoc Analysis of a Randomized Trial.

INTRODUCTION: Axial length (AL) elongation in myopia is considered irreversible. We aimed to systemically report unexpected AL shortening observed in a randomized clinical trial (RCT) after repeated low-level red-light (RLRL) therapy. METHODS: This is a post hoc analysis of a multicenter, single-masked RCT. Two hundred sixty-four myopic children aged 8-13 years allocated to RLRL treatment (intervention group) or a single vision spectacle (SVS, control group) were included. AL was measured using an IOL-master 500 at baseline, 1-, 3-, 6-, and 12-month follow-up visits. AL shortening was defined as AL reduction from baseline to follow-up visits at three cutoffs: > 0.05 mm, > 0.10 mm, and > 0.20 mm. Frequency of AL shortening at different cutoffs was calculated. Analysis was done with intent to treat (ITT). RESULTS: At 12-months follow up, frequency of AL shortening > 0.05 mm was 26/119 (21.85%) and 2/145 (1.38%) for the RLRL group versus the control group, respectively. The frequency was 18/119 (15.13%) versus 0/145 (0%) for AL shortening > 0.10 mm, and 7/119 (5.88%) versus 0/145 (0%), for AL shortening > 0.20 mm, respectively (p < 0.001). Mean AL shortening after 12 months (SD) was -0.156 (0.086) mm in the RLRL group and -0.06 mm in the control group. Age was significantly associated with AL shortening in the multivariable analysis. For the RLRL group that exhibited AL shortening (n = 56), choroidal thickness (ChT) thickening (0.056 mm) could only explain 28.3% of AL shortening (-0.20 mm). CONCLUSION: Nearly a quarter of children had > 0.05 mm AL shortening following 12 months of RLRL therapy, whereas AL shortening rarely occurred among controls. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04073238).

Design and Baseline Data of the Diabetes Registration Study: Guangzhou Diabetic Eye Study.

PURPOSE: The incidence and risk factors for diabetic retinopathy (DR) in southern China remain unclear. This project aims to explore the onset and progression of DR and their determinants through a prospective cohort in South China. METHODS: The Guangzhou Diabetic Eye Study (GDES) recruited patients with type 2 diabetic registered in the community health centers in Guangzhou, China. Comprehensive examinations were performed including visual acuity, refraction, ocular biometry, fundus imaging, blood and urine tests. RESULTS: A total of 2305 eligible patients were included in the final analysis. In total, 14.58% of the participants had any DR and 4.25% had vision-threatening DR (VTDR), among which 76 (3.30%), 197 (8.55%), 45 (1.95%) and 17 (0.74%) were classified as mild NPDR, moderate NPDR, severe NPDR and PDR, respectively. There were 93 (4.03%) patients with diabetic macular edema (DME). The presence of any DR was independently associated with a longer duration of DM, higher degree of HbA1c, insulin treatment, higher average arterial pressure, higher concentration of serum creatinine, presence of urinary microalbumin, older age, and lower body mass index (BMI) (all p < 0.001). For VTDR, seven factors were significant: older age, a longer duration of DM, higher concentration of HbA1c, use of insulin, lower BMI, higher concentration of serum creatinine, and high albuminuria (all p < 0.05). These factors were also independently associated with DME (all p < 0.001). CONCLUSION: The GDES is the first large-scale prospective cohort study of the diabetic population in southern China, which will help to identify novel imaging and genetic biomarkers for DR in this population.

Retinal nerve fiber layer thinning as a novel fingerprint for cardiovascular events: results from the prospective cohorts in UK and China.

BACKGROUND: Retinal structural abnormalities have been found to serve as biomarkers for cardiovascular disease (CVD). However, the association between retinal nerve fiber layer (RNFL) thickness and the incidence of CVD events remains inconclusive, and relevant longitudinal studies are lacking. Therefore, we aimed to examine this link in two prospective cohort studies. METHODS: A total of 25,563 participants from UK Biobank who were initially free of CVD were included in the current study. Another 635 participants without retinopathy at baseline from the Chinese Guangzhou Diabetes Eye Study (GDES) were adopted as the validation set. Measurements of RNFL thickness in the macular (UK Biobank) and peripapillary (GDES) regions were obtained from optical coherence tomography (OCT). Adjusted hazard ratios (HRs), odd ratios (ORs), and 95% confidence intervals (CI) were calculated to quantify CVD risk. RESULTS: Over a median follow-up period of 7.67 years, 1281 (5.01%) participants in UK Biobank developed CVD events. Each 5-µm decrease in macular RNFL thickness was associated with an 8% increase in incident CVD risk (HR = 1.08, 95% CI: 1.01-1.17, p = 0.033). Compared with participants in the highest tertile of RNFL thickness, the risk of incident CVD was significantly increased in participants in the lowest thickness tertile (HR = 1.18, 95% CI: 1.01-1.38, p = 0.036). In GDES, 29 (4.57%) patients developed CVD events within 3 years. Lower average peripapillary RNFL thickness was also associated with a higher CVD risk (OR = 1.35, 95% CI: 1.11-1.65, p = 0.003). The additive net reclassification improvement (NRI) was 21.8%, and the absolute NRI was 2.0% by addition of RNFL thickness over the Framingham risk score. Of 29 patients with incident CVD, 7 were correctly reclassified to a higher risk category while 1 was reclassified to a lower category, and 21 high risk patients were not reclassified. CONCLUSIONS: RNFL thinning was independently associated with increased incident cardiovascular risk and improved reclassification capability, indicating RNFL thickness derived from the non-invasive OCT as a potential retinal fingerprint for CVD event across ethnicities and health conditions. TRIAL REGISTRATION: ISRCTN 15853192.

The Association between Dietary Iron Intake and Incidence of Dementia in Adults Aged 60 Years or over in the UK Biobank.

Background Several studies have investigated the association between dietary iron intake and cognitive impairment, but little is known about the relationship between iron intake and dementia incidence. Objectives This study explored the association between dietary iron intake and incident dementia in males and females. Whether this association was modified by factors such as age and medical diseases was also examined. Methods We included 41,213 males and 48,892 females aged 60 years or over, from the UK-Biobank cohort. Dietary iron intake was measured using a web-based 24-h dietary recall questionnaire from between 2009 and 2012. Incident dementia was ascertained using hospital inpatient records and death registers until April 2021. Cox proportional regression models examined the association between iron intake and incident dementia, and hazard ratio curves were constructed with knots from the analysis indicating insufficient or excessive iron intake. Results During a mean follow-up of 11.8 years, 560 males and 492 females developed dementia. A non-linear relationship between iron intake and incident dementia was observed in both males and females. The lowest incidence rates were observed in the higher iron intake quintile (Q4: ≥15.73, <17.57 mg/day) for males, and the intermediate iron intake quintile (Q3: ≥12.4, <13.71 mg/day) for females. Among those aged 60 and above, all-cause dementia in males was associated with deficient iron intake (Q1 versus Q4: Hazard ratio [HR]: 1.37, 95% Confidence interval [95%CI]: 1.01−1.86, p = 0.042) and excessive iron intake (Q5 versus Q4: HR: 1.49, 95%CI: 1.14−1.96, p = 0.003), whilst significant associations between all-cause dementia and deficient iron intake were only observed in females without hypertension. Smoking status was a significant moderator (p-value for trend = 0.017) for dementia in males only. Conclusions Excessive iron intake (≥17.57 mg/day) is associated with a higher incidence of all-cause dementia in males and smoking status modified this association amongst males. Deficient iron intake (<10.93 mg/day) was associated with a higher incidence of all-cause dementia in females without a history of hypertension.

Clinically Significant Axial Shortening in Myopic Children After Repeated Low-Level Red Light Therapy: A Retrospective Multicenter Analysis.

INTRODUCTION: Myopia is recognized as a progressive eye disease. The aim of this study was to evaluate the frequency and associated factors of clinically significant axial length (AL) shortening among myopic children following repeated low-level red light (RLRL) therapy. METHODS: The clinical data that were collected for the myopic children aged 3-17 years who received an RLRL therapy delivered by home-use desktop light device that emitted light at 650 nm for at least 1 year, were reviewed. The clinical data included AL, spherical equivalent refraction (SER), and visual acuity measured at baseline and follow-up. The primary outcomes were frequency of AL shortening of > 0.05 mm, > 0.10 mm, and > 0.20 mm per year, and associated factors of AL shortening per year. RESULTS: A total of 434 myopic children with at least 12 months of follow-up data were included. The mean age of participants was 9.7 (2.6) years with SER of -3.74 (2.60) diopters. There were 115 (26.50%), 76 (17.51%), and 20 (4.61%) children with AL shortening based on cutoffs of 0.05 mm/year, 0.10 mm/year, and 0.20 mm/year, respectively. In the multivariable model, AL shortening was significantly associated with older baseline age, female gender, and longer baseline AL or greater spherical equivalent refraction (all P < 0.05). Among AL shortened eyes, the mean AL difference (standard deviation, SD) was -0.142 (0.094) mm/year. Greater AL shortening was observed among children who were younger and had longer baseline AL (all P < 0.05). CONCLUSIONS: More than a quarter of children had AL shortening > 0.05 mm following RLRL therapy, and the overall mean AL change was -0.142 mm/year. Further studies should explore the mechanisms underlying AL shortening.

Effects of Blood Pressure and Arterial Stiffness on Retinal Neurodegeneration: Cross-Sectional and Longitudinal Evidence From UK Biobank and Chinese Cohorts.

BACKGROUND: Hypertension might be a modifiable risk factor for neurodegeneration diseases. However, the associations between blood pressure (BP), arterial stiffness index and retinal neurodegeneration remain unclear. METHODS: This study used cross-sectional data from the United Kingdom BioBank (UKB) and longitudinal data from the Chinese Ocular Imaging Project (COIP). The macular ganglion cell-inner plexiform layer thickness (mGCIPLT) and macular retinal nerve fiber layer thickness were measured using spectral domain optical coherence tomography imaging. Swept-source optical coherence tomography was performed to obtain the longitudinal trajectory of the mGCIPLT and peripapillary retinal nerve fiber layer thickness in the COIP cohort. Multivariable linear models were used to analyze the associations between BP and retinal measurements. RESULTS: In a cross-sectional analysis of 22 801 participants from UKB, thinner mGCIPLT was related to higher systolic BP (ß: -0.103 [-0.146 to -0.061]; P<0.001), and higher diastolic BP (ß: -0.191 [-0.265 to -0.117]; P<0.001), and was significantly associated with higher mean arterial pressure (ß: -0.174 [-0.238 to -0.109]; P<0.001) and higher mean pulse pressure (ß: -0.080 [-0.139 to -0.020]; P=009). In a longitudinal analysis of 2012 eligible COIP participants, higher levels of baseline systolic BP, diastolic BP, mean arterial pressure, and mean pulse pressure were associated with faster thinning in mGCIPLT and peripapillary retinal nerve fiber layer thickness (all P<0.001). The strongest association was the effect of mean arterial pressure on mGCIPLT (ß: -0.118 [-0.175 to -0.061]; P<0.001). The results of the analysis of macular retinal nerve fiber layer thickness and peripapillary retinal nerve fiber layer thickness were consistent with those of mGCIPLT. CONCLUSIONS: BP levels were independently and consistently associated with various retinal neurodegenerative exacerbations.

Leading mediators of sex differences in the incidence of dementia in community-dwelling adults in the UK Biobank: a retrospective cohort study.

BACKGROUND: Little is known regarding whether sex assigned at birth modifies the association between several predictive factors for dementia and the risk of dementia itself. METHODS: Our retrospective cohort study included 214,670 men and 214,670 women matched by age at baseline from the UK Biobank. Baseline data were collected between 2006 and 2010, and incident dementia was ascertained using hospital inpatient or death records until January 2021. Mediation analysis was tested for 133 individual factors. RESULTS: Over 5,117,381 person-years of follow-up, 5928 cases of incident all-cause dementia (452 cases of young-onset dementia, 5476 cases of late-onset dementia) were documented. Hazard ratios (95% CI) for all-cause, young-onset, and late-onset dementias associated with the male sex (female as reference) were 1.23 (1.17-1.29), 1.42 (1.18-1.71), and 1.21 (1.15-1.28), respectively. Out of 133 individual factors, the strongest mediators for the association between sex and incident dementia were multimorbidity risk score (percentage explained (95% CI): 62.1% (45.2-76.6%)), apolipoprotein A in the blood (25.5% (15.2-39.4%)), creatinine in urine (24.9% (16.1-36.5%)), low-density lipoprotein cholesterol in the blood (23.2% (16.2-32.1%)), and blood lymphocyte percentage (21.1% (14.5-29.5%)). Health-related conditions (percentage (95% CI) explained: 74.4% (51.3-88.9%)) and biomarkers (83.0% (37.5-97.5%)), but not lifestyle factors combined (30.1% (20.7-41.6%)), fully mediated sex differences in incident dementia. Health-related conditions combined were a stronger mediator for late-onset (75.4% (48.6-90.8%)) than for young-onset dementia (52.3% (25.8-77.6%)), whilst lifestyle factors combined were a stronger mediator for young-onset (42.3% (19.4-69.0%)) than for late-onset dementia (26.7% (17.1-39.2%)). CONCLUSIONS: Our analysis matched by age has demonstrated that men had a higher risk of all-cause, young-onset, and late-onset dementias than women. This association was fully mediated by health-related conditions or blood/urinary biomarkers and largely mediated by lifestyle factors. Our findings are important for understanding potential mechanisms of sex in dementia risk.

Contrastive pre-training and linear interaction attention-based transformer for universal medical reports generation.

Interpreting medical images such as chest X-ray images and retina images is an essential step for diagnosing and treating relevant diseases. Proposing automatic and reliable medical report generation systems can reduce the time-consuming workload, improve efficiencies of clinical workflows, and decrease practical variations between different clinical professionals. Many recent approaches based on image-encoder and language-decoder structure have been proposed to tackle this task. However, some technical challenges remain to be solved, including the fusion efficacy between the language and visual cues and the difficulty of obtaining an effective pre-trained image feature extractor for medical-specific tasks. In this work, we proposed the weighted query-key interacting attention module, including both the second-order and first-order interactions. Compared with the conventional scaled dot-product attention, this design generates a strong fusion mechanism between language and visual signals. In addition, we also proposed the contrastive pre-training step to reduce the domain gap between the image encoder and the target dataset. To test the generalizability of our learning scheme, we collected and verified our model on the world-first multi-modality retina report generation dataset referred to as Retina ImBank and another large-scale retina Chinese-based report dataset referred to as Retina Chinese. These two datasets will be made publicly available and serve as benchmarks to encourage further research exploration in this field. From our experimental results, we demonstrate that our proposed method has outperformed multiple state-of-the-art image captioning and medical report generation methods on IU X-RAY, MIMIC-CXR, Retina ImBank, and Retina Chinese datasets.

Evaluation of Systemic Medications Associated With Surgically Treated Cataract Among US Adults.

PURPOSE: To comprehensively determine the associations between systemic medications and surgically treated cataract in the US population. DESIGNS: Retrospective cross-sectional study. METHODS: Participants aged ≥40 years from the 1999-2008 National Health and Nutrition Examination Survey (NHANES) were included. Surgically treated cataract was defined as cataract requiring a procedure. Data on prescription drug use over the past 30 days were collected via home interviews. Drug categories for ophthalmic indications and those prescribed in less than 0.5% of the participants were excluded from the analysis. Separate logistic regression models were used to explore associations between each drug category and surgically treated cataract. The Benjamin-Hochberg procedure was used to control the false discovery rate. RESULTS: A total of 14,931 were included in the present analysis. The weighted prevalence of surgically treated cataract was 9.6% (n=2010). We identified 20 drug categories that had significant associations with surgically treated cataract, of which 8 associations remained statistically significant after further adjustment for pertinent comorbidities. The 3 drug categories with the highest odds ratio (OR) values were tricyclic antidepressants (OR, 2.21; 95% CI, 1.38-3.51; P = .001), insulin (OR, 2.13; 95% CI, 1.48-3.07; P = 9.41×10-5) and group III antiarrhythmic agents (OR, 2.00; 95% CI, 1.25-3.19; P = .004). The use of sex hormone combinations among women reduced the risk of having surgically treated cataract (OR, 0.011; 95% CI, 0.001-0.089; P = 5.98×10-5). Dose-response relationships were observed for all 8 drug categories. CONCLUSIONS: Our comprehensive evaluation provides new knowledge on the complex relationships between systemic medications and surgically treated cataract.

Development and Validation of a Model to Predict Who Will Develop Myopia in the Following Year as a Criterion to Define Premyopia.

PURPOSE: To develop and validate models to predict who will develop myopia in the following year based on cycloplegic refraction or ocular biometry and to identify thresholds of premyopia. METHODS: Prospective longitudinal data of nonmyopic children at baseline from the Guangzhou Twins Eye Study and the Guangzhou Outdoor Activity Longitudinal Study were used as the training set, and the Singapore Cohort Study of the Risk factors for Myopia study formed the external validation set. Age, sex, cycloplegic refraction, ocular biometry, uncorrected visual acuity, and parental myopia were integrated into 3 logistic regression models to predict the onset of myopia in the following year. Premyopia cutoffs and an integer risk score system were derived based on the identified risk. RESULTS: In total, 2896 subjects with at least 2 visits were included. Cycloplegic refraction at baseline is a better predictor to identify the children with myopia onset [C-statistic=0.91, 95% confidence interval (CI), 0.87-0.94; C-statistic=0.92, 95% CI, 0.92-0.92 for internal and external validation, respectively], comparing to axial length, corneal curvature radius (CR) and anterior chamber depth (C-statistic=0.81, 95% CI, 0.73-0.88; C-statistic=0.80, 95% CI, 0.79-0.80, respectively), and axial length/CR (C-statistic=0.78, 95% CI, 0.71-0.85; C-statistic=0.76, 95% CI, 0.75-0.76). With a risk of >70%, the definitions of premyopia indicating approaching myopia onset were 0.00 D for 6-8 years and -0.25 D for ≥9 years in children with 2 myopic parents. CONCLUSIONS: Either cycloplegic refraction or ocular biometry can predict 1-year risk of myopia. Premyopia can be successfully defined through risk assessments based on children's age and predict who would require more aggressive myopia prophylaxis.

Prevalence and Risk Factors of Refractive Errors and Effective Spectacle Coverage in Emiratis and Non-Emiratis Aged 40 Years or Older: the Dubai Eye Health Survey.

PURPOSE: The aim was to investigate the prevalence and risk factors of refractive errors (REs) and the effective spectacle coverage in Emiratis and non-Emiratis in Dubai. DESIGN: The Dubai Eye Health Survey was a population-based cross-sectional study of participants aged 40 years or older. METHODS: Distance and near visual acuity (VA), and noncycloplegic automated refraction were tested according to a standardized protocol. Distance VA was tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR chart at 3 m and near VA was measured using the near vision logMAR chart at 40 cm under ambient lighting. Myopia was defined as spherical equivalent of refraction of less than -0.50 diopters (D), and hypermetropia as spherical equivalent of more than +0.50 D. Astigmatism was defined as cylinder power of 0.5 D or greater. Effective spectacle coverage for distance vision was computed as met need/(met need+unmet need+under-met need)×100%. Multivariable logistic regression models were used to examine associations between sociodemographic factors and RE. RESULTS: The authors included 892 participants (446 Emiratis and 446 non-Emiratis) in the analysis. The prevalence of hypermetropia was 20.4% [95% confidence interval (CI): 16.8%-24.4%] in Emiratis and 20.6% (95% CI: 20.0%-24.7%) in non-Emiratis. The prevalence of myopia and high myopia was 27.4% (95% CI: 23.3%-31.7%) and 1.8% (95% CI: 0.8%-3.5%) in Emiratis, and 19.5% (95% CI: 15.9%-23.5%) and 0.9% (95% CI: 0.2%-2.3%) in non-Emiratis, respectively. High education (P=0.02) and not currently working (P=0.002) were risk factors of myopia in non-Emiratis only. The prevalence of astigmatism was 7.4% (95% CI: 5.1%-10.2%) in Emiratis and 1.6% (95% CI: 0.6%-3.2%) in non-Emiratis. This prevalence was higher in individuals aged over 60 years (P<0.001) and men (P=0.014) among Emiratis. The prevalence of anisometropia and uncorrected presbyopia was 11.4% (95% CI: 8.6%-14.8%) and 0.7% (95% CI: 0.1%-2.0%) in Emiratis, and 9.2% (95% CI: 6.7%-12.3%) and 0.4% (95% CI: 0.05%-1.6%) in non-Emiratis, respectively. The effective spectacle coverage was 62.3% (95% CI: 54.0%-70.6%) and 69% (95% CI: 60.5%-77.5%) in Emiratis and non-Emiratis, respectively. CONCLUSIONS: A high proportion of Emiratis and non-Emiratis was affected by RE without optimal effective spectacle coverage, highlighting the imperativeness of intervention to alleviate the burden. The findings may help facilitate evidence-based policymaking concerning the delivery of eye care services and allocation of medical resources in Dubai.

Associations of vision impairment and eye diseases with frailty in community-dwelling older adults: a nationwide longitudinal study in China.

AIMS: To test whether vision impairment and major ophthalmic conditions are predictive of frailty. METHODS: The analysis included 5321 participants aged 60-95 years at baseline from the China Health and Retirement Longitudinal Study. Participants were enrolled in 2011 and followed up in 2013, and 2015 through a face-to-face interview. Distance/near vision impairment was defined by reporting poor eyesight and reporting excellent, very good, good or fair eyesight was used as the reference. A history of cataract surgery and glaucoma were also self-reported. Frailty was defined as the presence of ≥3 of the five components of the Fried phenotype: weakness, slowness, exhaustion, inactivity and shrinking. RESULTS: In the cross-sectional analysis, both near (odds ratio [OR] (95% confidence interval [CI]): 1.62 (1.30 to 2.00)) and distance (1.59 (1.30 to 1.96)) vision impairment was associated with a higher prevalence of frailty independent of confounders. In the longitudinal analysis, the multivariable-adjusted OR (95% CI) for incident frailty associated with glaucoma, distance vision impairment, near vision impairment and vision problem was 3.41 (1.46 to 7.99), 1.59 (1.17 to 2.17), 1.62 (1.17 to 2.23) and 2.11 (1.41 to 3.15), respectively. Vision problem was associated with decreased handgrip strength (ß (95% CI): -1.47 (-2.20 to -0.75) kg) during follow-up. Individuals with glaucoma (-0.11 (-0.16 to -0.05) m/s), distance vision impairment (-0.02 (-0.03 to 0.00) m/s) or vision problem (-0.02 (-0.05 to 0.00) m/s) had decreased gait speed compared with the control group. CONCLUSIONS: Vision problem, vision impairment and glaucoma are important predictors of frailty in older adults.