Shared genetic aetiology of Alzheimer's disease and age-related macular degeneration by APOC1 and APOE genes.

Background: Alzheimer's disease (AD) and age-related macular degeneration (AMD) share similar pathological features, suggesting common genetic aetiologies between the two. Investigating gene associations between AD and AMD may provide useful insights into the underlying pathogenesis and inform integrated prevention and treatment for both diseases. Methods: A stratified quantile-quantile (QQ) plot was constructed to detect the pleiotropy among AD and AMD based on genome-wide association studies data from 17 008 patients with AD and 30 178 patients with AMD. A Bayesian conditional false discovery rate-based (cFDR) method was used to identify pleiotropic genes. UK Biobank was used to verify the pleiotropy analysis. Biological network and enrichment analysis were conducted to explain the biological reason for pleiotropy phenomena. A diagnostic test based on gene expression data was used to predict biomarkers for AD and AMD based on pleiotropic genes and their regulators. Results: Significant pleiotropy was found between AD and AMD (significant leftward shift on QQ plots). APOC1 and APOE were identified as pleiotropic genes for AD-AMD (cFDR <0.01). Network analysis revealed that APOC1 and APOE occupied borderline positions on the gene co-expression networks. Both APOC1 and APOE genes were enriched on the herpes simplex virus 1 infection pathway. Further, machine learning-based diagnostic tests identified that APOC1, APOE (areas under the curve (AUCs) >0.65) and their upstream regulators, especially ZNF131, ADNP2 and HINFP, could be potential biomarkers for both AD and AMD (AUCs >0.8). Conclusion: In this study, we confirmed the genetic pleiotropy between AD and AMD and identified APOC1 and APOE as pleiotropic genes. Further, the integration of multiomics data identified ZNF131, ADNP2 and HINFP as novel diagnostic biomarkers for AD and AMD.

Vedolizumab and Ustekinumab Levels in Pregnant Women With Inflammatory Bowel Disease and Infants Exposed In Utero.

BACKGROUND & AIMS: Vedolizumab and ustekinumab pharmacokinetics in pregnancy and the infant after in utero exposure remain incompletely defined. We aim to define the antenatal stability of ustekinumab and vedolizumab levels and the time at which infant drug levels become undetectable. METHODS: This multicenter prospective observational cohort study recruited pregnant or preconception women with inflammatory bowel disease receiving vedolizumab or ustekinumab. Trough drug levels, clinical data, and biochemical data were documented preconception, during each trimester of pregnancy, and postpartum. Maternal and cord blood drug levels were measured at delivery and in infants until undetectable. Infant outcomes were assessed until 2 years of age. RESULTS: A total of 102 participants (vedolizumab, n = 58) were included. The majority of mothers were, and remained, in clinical and biochemical remission. Maternal vedolizumab levels decreased over the course of pregnancy in association with increasing weight, rather than increasing gestation. Maternal ustekinumab levels remained stable. The median time to drug becoming undetectable in the infant was shorter for vedolizumab (11 wk; range, 5-19 wk; n = 32) than ustekinumab (14 wk; range, 9-36 wk; n = 17) and correlated positively with infant delivery level. Thirty-two of 41 (88%) and 17 of 30 (67%) vedolizumab- and ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age, respectively. Pregnancy and infant outcomes were favorable. Twenty infants with undetectable drug levels received the rotavirus vaccine, with no adverse reactions reported. CONCLUSIONS: Maternal vedolizumab levels decreased, whereas ustekinumab levels remained stable over the course of pregnancy. Most vedolizumab- and approximately half of ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age. No concerning maternal or infant safety signals were identified.

Treatment satisfaction with Omnipod DASH in adults with type 1 diabetes: A non-blinded 1:1 randomized controlled trial.

OBJECTIVE: We compared treatment satisfaction with a tubeless insulin pump (Omnipod DASH® Insulin Management System) to usual care (multiple daily injections [MDI] or tubed insulin pump therapy [IPT]) in adults with type 1 diabetes using self-monitoring blood glucose (SMBG). RESEARCH DESIGN AND METHODS: Adults with type 1 diabetes on MDI (n = 40) or IPT (n = 25) from four diabetes centers in Australia were randomized in a 1:1 non-blinded manner to Omnipod DASH System (Omnipod group) or continue usual care (Usual Care group) for 12 weeks, followed by a further 12-week extension where all participants used the device. The primary outcome was treatment satisfaction assessed by change in Diabetes Technology Questionnaire 'current' (ΔDTQ-current) score at 12-weeks (study-end). Secondary outcomes included ΔDTQ-current following extension and other participant-reported outcomes (PROs) measuring quality of life, burden of disease treatment, glycemic and device-related outcomes at 12-weeks (study-end) and 24-weeks (end-extension). RESULTS: Treatment satisfaction improved more in Omnipod group vs. Usual Care group (ΔDTQ-current score of 16.4 [21.2] vs. 0.0 [12.8]; p < 0.001) at study-end. Significantly greater improvements in other PROs and HbA1c were also observed. Improvements in DTQ-current and other PROs comparing study-end and end-extension were similar. While %TIR change from baseline did not differ at study-end (-2.0 [12.7] %), it was significantly greater at end-extension (5.6 [10.9] %; p = 0.016). CONCLUSIONS: Omnipod DASH System resulted in greater treatment satisfaction at 12 weeks in adults with type 1 diabetes using SMBG which was sustained after 24 weeks of device use without compromising sleep quality and fear of hypoglycemia. Improvements in glycemia were also observed.

"You can hide it if you want to, you can let it be seen if you want to": A qualitative study of the lived experiences of Australian adults with type 1 diabetes using the Omnipod DASH® system.

AIMS: Understanding the lived experience of using a tubeless insulin pump and how this differs compared to usual care (tubed insulin pump therapy (IPT) vs multiple daily injections (MDI)). METHODS: Interviews were conducted after 12-weeks of using the Omnipod DASH Insulin Management System (Insulet, Acton, MA) and analysed using thematic analysis. RESULTS: Fifty-eight adults (35 female; mean age 42;SD 13 years; 35 previous MDI) were interviewed. Most (84 %) wanted to continue using the device. Experiences fit two themes: 1. Taking back control of my diabetes: many previous MDI users perceived improved glycaemic control, explained by more "nuanced" control, with some reporting positive effects during exercise and sleep. Many previous MDI and IPT users endorsed positive experiences in concealing or disclosing their diabetes to others. However, some previous MDI users reported negative psychosocial experiences due to feeling continuously "attached" to their diabetes. 2. Barriers and facilitators of device acceptability: both MDI and IPT users cited wearability, alarms and the financial cost impacted their choice to continue device use. IPT users reported positive wearability experiences. CONCLUSIONS: The tubeless pump improved diabetes management perceptions for both MDI and tubed pump users. However, participants' prior glucose management affected perceptions of its advantages and disadvantages.

Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort study.

BACKGROUND: Little is known regarding the leading risk factors for dementia/Alzheimer's disease (AD) in individuals with and without APOE4. The identification of key risk factors for dementia/Alzheimer's disease (AD) in individuals with and without the APOE4 gene is of significant importance in global health. METHODS: Our analysis included 110,354 APOE4 carriers and 220,708 age- and sex-matched controls aged 40-73 years at baseline (between 2006-2010) from UK Biobank. Incident dementia was ascertained using hospital inpatient, or death records until January 2021. Individuals of non-European ancestry were excluded. Furthermore, individuals without medical record linkage were excluded from the analysis. Moderation analysis was tested for 134 individual factors. RESULTS: During a median follow-up of 11.9 years, 4,764 cases of incident all-cause dementia and 2065 incident AD cases were documented. Hazard ratios (95% CIs) for all-cause dementia and AD associated with APOE4 were 2.70(2.55-2.85) and 3.72(3.40-4.07), respectively. In APOE4 carriers, the leading risk factors for all-cause dementia included low self-rated overall health, low household income, high multimorbidity risk score, long-term illness, high neutrophil percentage, and high nitrogen dioxide air pollution. In non-APOE4 carriers, the leading risk factors included high multimorbidity risk score, low overall self-rated health, low household income, long-term illness, high microalbumin in urine, high neutrophil count, and low greenspace percentage. Population attributable risk for these individual risk factors combined was 65.1%, and 85.8% in APOE4 and non-APOE4 carriers, respectively. For 20 risk factors including multimorbidity risk score, unhealthy lifestyle habits, and particulate matter air pollutants, their associations with incident dementia were stronger in non-APOE4 carriers. For only 2 risk factors (mother's history of dementia, low C-reactive protein), their associations with incident all-cause dementia were stronger in APOE4 carriers. CONCLUSIONS: Our findings provide evidence for personalized preventative approaches to dementia/AD in APOE4 and non-APOE4 carriers. A mother's history of dementia and low levels of C-reactive protein were more important risk factors of dementia in APOE4 carriers whereas leading risk factors including unhealthy lifestyle habits, multimorbidity risk score, inflammation and immune-related markers were more predictive of dementia in non-APOE4 carriers.

A pilot randomised controlled parallel arm trial evaluating treatment satisfaction with the Omnipod DASH® Insulin Management System compared with usual care in adults with type 1 diabetes in Australia: rationale, study design and methodologies.

BACKGROUND: Insulin pump therapy (IPT) improves glucose control in people with type 1 diabetes (T1D) compared with multiple daily injections (MDI). However, their size, the tethered insulin infusion set, intrusiveness when operating the device and the need to disconnect during showering limit their acceptance to many who may benefit. The Omnipod DASH® Insulin Management System is a small waterproof tubeless device which is wirelessly controlled by a handheld device which may be an acceptable alternative. However, there are no randomised controlled trials focusing on the impact on user perceptions of tubeless insulin pump therapy. This pilot study aims to assess study feasibility and acceptability of patch pump therapy compared with usual care in adults with T1D in Australia to inform power calculations and progression to a large-scale multi-site randomised controlled study. METHODS: A pilot multi-site parallel randomised controlled study will be conducted in sixty-four adults with T1D who are managed on MDI or IPT and self-monitoring with finger-stick blood glucose from four specialist diabetes centres in Victoria, Australia. Following carbohydrate counting education, participants will be randomised to use Omnipod DASH® System (Omnipod group) or continue usual care (usual care group) for 12 weeks, followed by a 12-week extension phase where all participants will use Omnipod DASH® System. The primary outcome measure is feasibility determined by study completion rates with a threshold of 0.80. Acceptability of the intervention (Omnipod DASH® System) will be assessed by the difference in Diabetes Technology Questionnaire 'current' (DTQ-current) score at 12 weeks post-randomisation compared to baseline. Secondary outcomes will include other measures of user acceptance, process outcomes, resource outcomes, participant-centred outcomes, healthcare professional perceptions and glycaemic outcomes. DISCUSSION: This pilot study will provide insights regarding the feasibility of the study design and the first data regarding user acceptance of insulin patch pump technology in Australian T1D adults. We anticipate that this study will provide information informing the design of a larger study evaluating the impact of patch pumps on subjective outcomes that are of significance to the person living with T1D. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( https://anzctr.org.au/ ) ACTRN12621001195842 (8th September 2021). Please refer to Additional file 1: Appendix 1 for full details.

A Systematic Review and Meta-Analysis of Applying Deep Learning in the Prediction of the Risk of Cardiovascular Diseases From Retinal Images.

Purpose: The purpose of this study was to perform a systematic review and meta-analysis to synthesize evidence from studies using deep learning (DL) to predict cardiovascular disease (CVD) risk from retinal images. Methods: A systematic literature search was performed in MEDLINE, Scopus, and Web of Science up to June 2022. We extracted data pertaining to predicted outcomes, model development, and validation and model performance metrics. Included studies were graded using the Quality Assessment of Diagnostic Accuracies Studies 2 tool. Model performance was pooled across eligible studies using a random-effects meta-analysis model. Results: A total of 26 studies were included in the analysis. There were 42 CVD risk-related outcomes predicted from retinal images were identified, including 33 CVD risk factors, 4 cardiac imaging biomarkers, 2 CVD risk scores, the presence of CVD, and incident CVD. Three studies that aimed to predict the development of future CVD events reported an area under the receiver operating curve (AUROC) between 0.68 and 0.81. Models that used retinal images as input data had a pooled mean absolute error of 3.19 years (95% confidence interval [CI] = 2.95-3.43) for age prediction; a pooled AUROC of 0.96 (95% CI = 0.95-0.97) for gender classification; a pooled AUROC of 0.80 (95% CI = 0.73-0.86) for diabetes detection; and a pooled AUROC of 0.86 (95% CI = 0.81-0.92) for the detection of chronic kidney disease. We observed a high level of heterogeneity and variation in study designs. Conclusions: Although DL models appear to have reasonably good performance when it comes to predicting CVD risk, further work is necessary to evaluate the real-world applicability and predictive accuracy. Translational Relevance: DL-based CVD risk assessment from retinal images holds great promise to be translated to clinical practice as a novel approach for CVD risk assessment, given its simple, quick, and noninvasive nature.

EBD: an eye biomarker database.

MOTIVATION: Many ophthalmic disease biomarkers have been identified through comprehensive multiomics profiling, and hold significant potential in advancing the diagnosis, prognosis, and management of diseases. Meanwhile, the eye itself serves as a natural biomarker for several systemic diseases including neurological, renal, and cardiovascular systems. We aimed to collect and standardize this eye biomarkers information and construct the eye biomarker database (EBD) to provide ophthalmologists with a platform to search, analyze, and download these eye biomarker data. RESULTS: In this study, we present the EBD , a world-first online compilation comprising 889 biomarkers for 26 ocular diseases and 939 eye biomarkers for 181 systemic diseases. The EBD also includes the information of 78 "nonbiomarkers"-the objects that have been proven cannot be biomarkers. Biological function and network analysis were conducted for these ocular disease biomarkers, and several hub pathways and common network topology characteristics were newly identified, which may promote future ocular disease biomarker discovery and characterizes the landscape of biomarkers for eye diseases at the pathway and network level. The EBD is expected to yield broader utility among developmental biologists and clinical scientists in and outside of the eye field by assisting in the identification of biomarkers linked to eye disorders and related systemic diseases. AVAILABILITY AND IMPLEMENTATION: EBD is available at http://www.eyeseeworld.com/ebd/index.html.

Optic Nerve Head Capillary Network Quantified by Optical Coherence Tomography Angiography and Decline of Renal Function in Type 2 Diabetes: A Three-Year Prospective Study.

PURPOSE: To assess the association of optic capillary perfusion with decline in the estimated glomerular filtration rate (eGFR) and to clarify its added value. DESIGN: Prospective, observational cohort study. METHODS: Patients with type 2 diabetes mellitus without diabetic retinopathy (non-DR) underwent standardized examinations annually during a 3-year follow-up period. The superficial capillary plexus (SCP), deep capillary plexus (DCP), and radial peripapillary plexus (RPC) of optic nerve head (ONH) were visualized using optical coherence tomography angiography (OCTA), and the perfusion density (PD) and vascular density were quantified for the whole image and circumpapillary regions of the ONH.  The lowest tercile of annual eGFR slope was defined as the rapidly progressive group, and the highest tercile was considered the stable group. RESULTS: A total of 906 patients were included for 3-mm × 3-mm OCTA analysis. After adjusting for other confounders, each 1% decrease in baseline whole en face PD in SCP and RPC was associated with accelerated rates of decline in eGFR by -0.53 mL/min/1.73/m2 per year (95% confidence interval [CI] -0.17 to -0.90; P = .004) and -0.60 mL/min/1.73/m2 per year (95% CI 0.28-0.91), respectively. Adding both whole-image PD in SCP and whole-image PD in RPC to the conventional model increased the area under the curve from 0.696 (95% CI 0.654-0.737) to 0.725 (95% CI 0.685-0.765; P = .031). Another cohort of 400 eligible patients with 6-mm × 6 mm OCTA imaging validated the significant associations between ONH perfusion and rate of eGFR decline (P < .05). CONCLUSIONS: Reduced capillary perfusion of ONH in patients with type 2 diabetes mellitus is associated with a greater eGFR decline, and it has additional predictive value for detecting an early stage and progression.

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.

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.

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.

Association of Retinal Age Gap and Risk of Kidney Failure: A UK Biobank Study.

RATIONALE & OBJECTIVE: The incidence of kidney failure is known to increase with age. We have previously developed and validated the use of retinal age based on fundus images as a biomarker of aging. However, the association of retinal age with kidney failure is not clear. We investigated the association of retinal age gap (the difference between retinal age and chronological age) with future risk of kidney failure. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 11,052 UK Biobank study participants without any reported disease for characterizing retinal age in a deep learning algorithm. 35,864 other participants with retinal images and no kidney failure were followed to assess the association between retinal age gap and the risk of kidney failure. EXPOSURE: Retinal age gap, defined as the difference between model-based retinal age and chronological age. OUTCOME: Incident kidney failure. ANALYTICAL APPROACH: A deep learning prediction model used to characterize retinal age based on retinal images and chronological age, and Cox proportional hazards regression models to investigate the association of retinal age gap with incident kidney failure. RESULTS: After a median follow-up period of 11 (IQR, 10.89-11.14) years, 115 (0.32%) participants were diagnosed with incident kidney failure. Each 1-year greater retinal age gap at baseline was independently associated with a 10% increase in the risk of incident kidney failure (HR, 1.10 [95% CI, 1.03-1.17]; P=0.003). Participants with retinal age gaps in the fourth (highest) quartile had a significantly higher risk of incident kidney failure compared with those in the first quartile (HR, 2.77 [95% CI, 1.29-5.93]; P=0.009). LIMITATIONS: Limited generalizability related to the composition of participants in the UK Biobank study. CONCLUSIONS: Retinal age gap was significantly associated with incident kidney failure and may be a promising noninvasive predictive biomarker for incident kidney failure.

Retinal age gap as a predictive biomarker of stroke risk.

BACKGROUND: The aim of this study is to investigate the association of retinal age gap with the risk of incident stroke and its predictive value for incident stroke. METHODS: A total of 80,169 fundus images from 46,969 participants in the UK Biobank cohort met the image quality standard. A deep learning model was constructed based on 19,200 fundus images of 11,052 disease-free participants at baseline for age prediction. Retinal age gap (retinal age predicted based on the fundus image minus chronological age) was generated for the remaining 35,917 participants. Stroke events were determined by data linkage to hospital records on admissions and diagnoses, and national death registers, whichever occurred earliest. Cox proportional hazards regression models were used to estimate the effect of retinal age gap on risk of stroke. Logistic regression models were used to estimate the predictive value of retinal age and well-established risk factors in 10-year stroke risk. RESULTS: A total of 35,304 participants without history of stroke at baseline were included. During a median follow-up of 5.83 years, 282 (0.80%) participants had stroke events. In the fully adjusted model, each one-year increase in the retinal age gap was associated with a 4% increase in the risk of stroke (hazard ratio [HR] = 1.04, 95% confidence interval [CI]: 1.00-1.08, P = 0.029). Compared to participants with retinal age gap in the first quintile, participants with retinal age gap in the fifth quintile had significantly higher risks of stroke events (HR = 2.37, 95% CI: 1.37-4.10, P = 0.002). The predictive capability of retinal age alone was comparable to the well-established risk factor-based model (AUC=0.676 vs AUC=0.661, p=0.511). CONCLUSIONS: We found that retinal age gap was significantly associated with incident stroke, implying the potential of retinal age gap as a predictive biomarker of stroke risk.

Sustained and rebound effect of repeated low-level red-light therapy on myopia control: A 2-year post-trial follow-up study.

BACKGROUND: To evaluate the long-term efficacy and safety of continued repeated low-level red-light (RLRL) therapy on myopia control over 2 years, and the potential rebound effect after treatment cessation. METHODS: The Chinese myopic children who originally completed the one-year randomised controlled trial were enrolled. Children continued RLRL-therapy were defined as RLRL-RLRL group, while those who stopped and switched to single-vision spectacle (SVS) in the second year were RLRL-SVS group. Likewise, those who continued to merely wear SVS or received additional RLRL-therapy were SVS-SVS and SVS-RLRL groups, respectively. RLRL-therapy was provided by an at-home desktop light device emitting red-light of 650 nm and was administered for 3 min at a time, twice a day and 5 days per week. Changes in axial length (AL) and cycloplegic spherical equivalence refraction (SER) were measured. RESULTS: Among the 199 children who were eligible, 138 (69.3%) children attended the examination and 114 (57.3%) were analysed (SVS-SVS: n = 41; SVS-RLRL: n = 10; RLRL-SVS: n = 52; RLRL-RLRL: n = 11). The baseline characteristics were balanced among four groups. In the second year, the mean changes in AL were 0.28 ± 0.14 mm, 0.05 ± 0.24 mm, 0.42 ± 0.20 mm and 0.12 ± 0.16 mm in SVS-SVS, SVS-RLRL, RLRL-SVS and RLRL-RLRL group, respectively (p < 0.001). The respective mean SER changes were -0.54 ± 0.39D, -0.09 ± 0.55D, -0.91 ± 0.48D, and -0.20 ± 0.56D (p < 0.001). Over the 2-year period, axial elongation and SER progression were smallest in RLRL-RLRL group (AL: 0.16 ± 0.37 mm; SER: -0.31 ± 0.79D), followed by SVS-RLRL (AL: 0.44 ± 0.37 mm; SER: -0.96 ± 0.70D), RLRL-SVS (AL: 0.50 ± 0.28 mm; SER: -1.07 ± 0.69D) and SVS-SVS group (AL: 0.64 ± 0.29 mm; SER: -1.24 ± 0.63D). No self-reported adverse events, functional or structural damages were noted. CONCLUSIONS: Continued RLRL therapy sustained promising efficacy and safety in slowing myopia progression over 2 years. A modest rebound effect was noted after treatment cessation.

Diabetes mellitus and incident glaucoma in Australia: a 10-year cohort study from the 45 and Up Study.

Background: Understanding the relationship between diabetes mellitus (DM) and the severity of glaucoma is important for the primary prevention of incident glaucoma. This paper aims to examine the association between DM and incident glaucoma. Methods: The 45 and Up Study is a prospective cohort study where Australians aged ≥45 years old were enrolled. The incident of glaucoma at follow-up is the main outcome measured. Glaucoma incidence was identified as those with recorded glaucoma-related medication from the Pharmaceutical Benefits Scheme or surgery recorded in the Medicare Benefits Schedule. Patients with glaucoma were classified into the medical glaucoma group (with glaucoma-related medication but not surgery) and the surgical glaucoma group (with glaucoma-related surgery). A Cox regression model was used to calculate the hazard ratios (HRs) to examine the association between baseline DM and the risk of developing glaucoma during the follow-up period. The reference groups are as follows: (I) non-DM participant; (II) participant with DM, duration between 0 and 5 years; (III) participant uses insulin. Results: A total of 255,547 eligible participants, with no glaucoma diagnosis at baseline, were included. During the follow-up period, 7,667 patients (3.0%) were identified as medical glaucoma only and 2,326 patients (0.9%) underwent glaucoma surgery. After controlling for confounders, baseline DM was associated with an increased risk of glaucoma in the medical glaucoma group only [hazard ratio (HR) =1.36, 95% confidence interval (CI) =1.07-1.72, P=0.002]. However, baseline DM (HR =0.97, 95% CI =0.57-1.65, P=0.979) was not associated with an increased risk of surgical glaucoma. Conclusions: DM was associated with an increased risk of medical glaucoma only, there was no association identified with surgical glaucoma in the Australian population recruited in the 45 and Up Study.

Telemedicine and delivery of ophthalmic care in rural and remote communities: Drawing from Australian experience.

Rural and remote communities in Australia are characterised by small but widely dispersed populations. This has been proven to be a major hurdle in access to medical care services with screening and treatment goals repeatedly being missed. Telemedicine in ophthalmology provides the opportunity to increase the availability of high quality and timely access to healthcare within. Recent years has also seen the introduction of artificial intelligence (AI) in ophthalmology, particularly in the screening of diseases. AI will hopefully increase the number of appropriate referrals, reduce travel time for patients and ensure timely triage given the low number of qualified optometrists and ophthalmologists. Telemedicine and AI has been introduced in a number of countries and has led to tremendous benefits and advantages when compared to standard practices. This paper summarises current practices in telemedicine and AI and the future of this technology in improving patient care in the field of ophthalmology.

Association between dual sensory impairment and risk of mortality: a cohort study from the UK Biobank.

BACKGROUND: Dual sensory impairment is affecting over 10% of older adults worldwide. However, the long-term effect of dual sensory impairment (DSI) on the risk of mortality remains controversial. We aim to investigate the impact of single or/and dual sensory impairment on the risk of mortality in a large population-based sample of the adult in the UK with 14-years of follow-up. METHODS: This population-based prospective cohort study included participants aged 40 and over with complete records of visual and hearing functions from the UK Biobank study. Measurements of visual and hearing functions were performed at baseline examinations between 2006 and 2010, and data on mortality was obtained by 2021. Dual sensory impairment was defined as concurrent visual and hearing impairments. Cox proportional hazards regression models were employed to evaluate the impact of sensory impairment (dual sensory impairment, single visual or hearing impairment) on the hazard of mortality. RESULTS: Of the 113,563 participants included in this study, the mean age (standard deviation) was 56.8 (8.09) years, and 61,849 (54.5%) were female. At baseline measurements, there were 733 (0.65%) participants with dual sensory impairment, 2,973 (2.62%) participants with single visual impairment, and 13,560 (11.94%) with single hearing impairment. After a follow-up period of 14 years (mean duration of 11 years), 5,992 (5.28%) participants died from all causes. Compared with no sensory impairment, dual sensory impairment was significantly associated with an estimated 44% higher hazard of mortality (hazard ratio: 1.44 [95% confidence interval, 1.11-1.88], p = 0.007) after multiple adjustments. CONCLUSIONS: Individuals with dual sensory impairment were found to have an independently 44% higher hazard of mortality than those with neither sensory impairment. Timely intervention of sensory impairment and early prevention of its underlying causes should help to reduce the associated risk of mortality.

Plasma metabolomic profiles of dementia: a prospective study of 110,655 participants in the UK Biobank.

BACKGROUND: Plasma metabolomic profile is disturbed in dementia patients, but previous studies have discordant conclusions. METHODS: Circulating metabolomic data of 110,655 people in the UK Biobank study were measured with nuclear magnetic resonance technique, and incident dementia records were obtained from national health registers. The associations between plasma metabolites and dementia were estimated using Cox proportional hazard models. The 10-fold cross-validation elastic net regression models selected metabolites that predicted incident dementia, and a 10-year prediction model for dementia was constructed by multivariable logistic regression. The predictive values of the conventional risk model, the metabolites model, and the combined model were discriminated by comparison of area under the receiver operating characteristic curves (AUCs). Net reclassification improvement (NRI) was used to estimate the change of reclassification ability when adding metabolites into the conventional prediction model. RESULTS: Amongst 110,655 participants, the mean (standard deviation) age was 56.5 (8.1) years, and 51 186 (46.3%) were male. A total of 1439 (13.0%) developed dementia during a median follow-up of 12.2 years (interquartile range: 11.5-12.9 years). A total of 38 metabolites, including lipids and lipoproteins, ketone bodies, glycolysis-related metabolites, and amino acids, were found to be significantly associated with incident dementia. Adding selected metabolites (n=24) to the conventional dementia risk prediction model significantly improved the prediction for incident dementia (AUC: 0.824 versus 0.817, p =0.042) and reclassification ability (NRI = 4.97%, P = 0.009) for identifying high risk groups. CONCLUSIONS: Our analysis identified various metabolomic biomarkers which were significantly associated with incident dementia. Metabolomic profiles also provided opportunities for dementia risk reclassification. These findings may help explain the biological mechanisms underlying dementia and improve dementia prediction.