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.

Scleral thinning causes, diagnosis, and management: A narrative review.

INTRODUCTION: Sclera forms the outer fibrous coat of the eye and provides structural integrity for the housing of intraocular contents. Scleral thinning is a serious progressive condition which can lead to perforation and worsening visual functioning. This review aims to summarize the anatomical consideration and causes of scleral thinning, diagnosis, and the various surgical approaches available to treat scleral thinning. MATERIALS AND METHODS: The narrative literature review was conducted by senior Ophthalmologists and researchers. PubMed, EMBASE, Web of Science, Scopus, and Google Scholar databases were searched for relevant literature from infinity till March 2022. Terms of the search referred to 'sclera' or 'scleral thinning' or 'scleral melting', and were combined with 'treatment', or 'management' or 'causes'. Publications were included in this manuscript if they offered information about the nature of these topics. Reference lists of relevant literature was searched. There were no limits on type of article to be included for this review. RESULTS: Scleral thinning arises from diverse congenital, degenerative, immunological, infectious, post-surgical, and traumatic etiologies. It is diagnosed upon slit-lamp examination, indirect ophthalmoscopy, and optical coherence tomography. Conservative pharmacological treatment of scleral thinning may include anti-inflammatory drugs, steroid drops, immunosuppressors, monoclonal antibodies, and surgical treatments including tarsorrhaphy, scleral transplantation, amniotic membrane transplantation, donor corneal graft, conjunctival flaps, tenon's membrane flap, pericardial graft, dermis graft, cadaveric dura mater graft, and other autologous and biological grafts. CONCLUSION: Scleral thinning treatments have developed dramatically in recent decades and the rise of alternative grafts for scleral transplantation procedures or use of conjunctival flaps have taken center stage in surgical management. This review adds a comprehensive summary of the scleral thinning with attention to the positive and negative features of new treatments alongside previous mainstay management strategies.

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.

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.

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.

The associations and mediators between visual disabilities and anxiety disorders in middle-aged and older adults: A population-based study.

Visual disabilities significantly impact an individual's mental health. Little is known about the prospective relationship between visual disabilities and anxiety disorders and the underlying effects of modifiable risk factors. Our analysis was based on 117,252 participants from the U.K. Biobank, with baseline data collected between 2006 and 2010. Habitual visual acuity was measured by a standardized logarithmic chart, and ocular disorders reported using questionnaires were collected at baseline. Incident hospitalized anxiety recorded using longitudinal linkage with hospital inpatient data, lifetime anxiety disorder, and current anxiety symptoms assessed by a comprehensive online mental health questionnaire were identified over a 10-year follow-up. After adjustments for confounding factors, one-line worse visual acuity (0.1 logarithm of the minimum angle of resolution [logMAR]) was associated with an increased risk of incident hospitalized anxiety (HR = 1.05, 95% CI = 1.01-1.08), lifetime anxiety disorder (OR = 1.07, 95% CI [1.01-1.12]), and current anxiety scores (ß = 0.028, 95% CI [0.002-0.054]). Besides poorer visual acuity, the longitudinal analysis also supported that each ocular disorder (including cataracts, glaucoma, macular degeneration, and diabetes-related eye disease) was significantly associated with at least two anxiety outcomes. Mediation analyses highlighted that subsequent onsets of eye diseases, especially cataracts, and lower socioeconomic status (SES) partly mediated the association between poorer visual acuity and anxiety disorders. This study demonstrates an overall association between visual disabilities and anxiety disorders in middle-aged and older adults. In particular, early interventions involving treatments for visual disabilities and effective psychological counseling services sensitive to socioeconomic status may help prevent anxiety in those living with poor vision. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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).

From bench to clinic: Emerging therapies for corneal scarring.

Corneal diseases are one of the leading causes of moderate-to-severe visual impairment and blindness worldwide, after glaucoma, cataract, and retinal disease in overall importance. Given its tendency to affect people at a younger age than other blinding conditions such as cataract and glaucoma, corneal scarring poses a huge burden both on the individuals and society. Furthermore, corneal scarring and fibrosis disproportionately affects people in poorer and remote areas, making it a significant ophthalmic public health problem. Traditional medical strategies, such as topical corticosteroids, are not effective in preventing fibrosis or scars. Corneal transplantation, the only effective sight-restoring treatment for corneal scars, is curbed by challenges including a severe shortage of tissue, graft rejection, secondary conditions, cultural barriers, the lack of well-trained surgeons, operating rooms, and well-equipped infrastructures. Thanks to tremendous research efforts, emerging therapeutic options including gene therapy, protein therapy, cell therapy and novel molecules are in development to prevent the progression of corneal scarring and compliment the surgical options currently available for treating established corneal scars in clinics. In this article, we summarise the most relevant preclinical and clinical studies on emerging therapies for corneal scarring in recent years, showing how these approaches may prevent scarring in its early development.

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.

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.

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.

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.

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.

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.

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.

Choriocapillaris flow deficit as a biomarker for diabetic retinopathy and diabetic macular edema: 3-year longitudinal cohort: Choriocapillaris flow predicts DR progression and DME development.

PURPOSE: To investigate the relationship between choriocapillaris flow deficit percentage (CC FD%) by swept-source optical coherence tomography angiography (SS-OCTA) and 3-year risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development. DESIGN: Prospective, observational cohort study. METHODS: A total of 903 participants with type 2 diabetes mellitus (T2DM) without DR or with mild non-proliferative DR (NPDR) free of DME at baseline were followed up annually for 3 years. All participants underwent standard 7-field fundus photography and spectral-domain OCT. SS-OCTA was used for retinal and choriocapillaris imaging and 3 × 3 mm2 macular CC FD% was quantified. Univariate and multivariate logistic models were used to evaluate the association between CC FD% and two or more steps of DR progression and DME development. The additional predictive value of CC FD% for outcome events was assessed using C-statistic, net reclassification index (NRI), and integrated discrimination improvement index (IDI). RESULTS: Over 3 years, 295 of 1805 eyes (16.34%) developed DR progression, and 118 eyes (6.54%) developed DME. A higher average CC FD% was correlated with DR progression (odds ratio [OR], 3.41 per SD increase, 95% confidence interval [CI]: 2.65-4.39, P<0.001) and DME development (OR, 1.37 per SD increase, 95% CI: 1.06-1.77, P=0.016) after adjusting for confounders. In the ETDRS regions, increased CC FD% in all fields was associated with DR progression; however, increased CC FD% in the inferior field was associated with DME development. Compared with the models based on established risk factors, the addition of average CC FD% significantly improved the C-statistics for DR progression (0.712 to 0.777, P<0.001) and DME occurrence (0.743 to 0.773, P=0.044). The estimated NRIs and IDIs (all >0) indicated that the addition of CC FD% led to a significant improvement in the discriminative performance for endpoints. CONCLUSION: CC FD% is independently associated with DR progression and DME development in the Chinese T2DM population and provides incremental predictive value beyond traditional risk factors and retinal microvascular parameters. Further inclusion of CC FD% in DR prediction models helps guide population-based screening and personalized management.

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.

Rates of choroidal loss and ganglion cell-inner plexiform layer thinning in type 2 diabetes mellitus and healthy individuals: a 2-year prospective study.

AIMS: To investigate longitudinal choroid and ganglion cell-inner plexiform layer (GCIPL) changes in type 2 diabetes mellitus (T2DM) patients and healthy populations across 2 years. METHODS: This prospective cohort study included T2DM patients and healthy controls. T2DM patients were divided into mild non-proliferative diabetic retinopathy (NPDR) or non-DR (NDR) groups. Macular choroidal and GCIPL thickness was measured using swept-source optical coherence tomography at baseline and follow-up after 2 years. A linear-mixed effect model compared rates of change in choroidal and GCIPL thicknesses between the three groups. RESULTS: 895 T2DM patients (770 in the NDR group and 125 in the NPDR group) and 847 healthy controls were included. Following 2 years, choroidal thinning occurred at a rate of -7.7±9.2 µm/year, -8.1±8.7 µm/year and -5.2±8.1 µm/year in NDR, NPDR and control groups, respectively (p<0.001). GCIPL loss occurred quickest in NPDR patients (-0.97±0.97 µm/year), followed by NDR (-0.91±0.89 µm/year) and the control group (-0.04±0.55 µm/year) (p<0.001). Following multivariate adjustment, choroidal thinning was -2.04 µm/year (95% CI: -4.05 to -0.03; p=0.047) and -1.95 µm/year (95% CI: -3.14 to -0.75; p=0.001) faster in NPDR and NDR groups than in the control group, respectively, and GCIPL thinning was -1.02 µm/year (95% CI: -1.19 to -0.84; p<0.001) and -0.88 µm/year (95% CI: -0.98 to -0.78; p<0.001) faster in the NPDR and NDR groups than in the control group, respectively. CONCLUSION: Progressive choroidal and GCIPL thinning occurs in healthy individuals and T2DM patients; however, T2DM undergoes accelerated choroidal and GCIPL loss in NPDR patients.