Long-Term Risk and Prediction of Progression in Primary Angle Closure Suspect.

Importance: Identifying primary angle closure suspect (PACS) eyes at risk of angle closure is crucial for its management. However, the risk of progression and its prediction are still understudied in long-term longitudinal studies about PACS. Objective: To explore baseline predictors and develop prediction models for the 14-year risk of progression from PACS to primary angle closure (PAC). Design, Setting, and Participants: This cohort study involved participants from the Zhongshan Angle Closure Prevention trial who had untreated eyes with PACS. Baseline examinations included tonometry, ultrasound A-scan biometry, and anterior segment optical coherence tomography (AS-OCT) under both light and dark conditions. Primary angle closure was defined as peripheral anterior synechiae in 1 or more clock hours, intraocular pressure (IOP) greater than 24 mm Hg, or acute angle closure. Based on baseline covariates, logistic regression models were built to predict the risk of progression from PACS to PAC during 14 years of follow-up. Results: The analysis included 377 eyes from 377 patients (mean [SD] patient age at baseline, 58.28 [4.71] years; 317 females [84%]). By the 14-year follow-up visit, 93 eyes (25%) had progressed from PACS to PAC. In multivariable models, higher IOP (odds ratio [OR], 1.14 [95% CI, 1.04-1.25] per 1-mm Hg increase), shallower central anterior chamber depth (ACD; OR, 0.81 [95% CI, 0.67-0.97] per 0.1-mm increase), and shallower limbal ACD (OR, 0.96 [95% CI, 0.93-0.99] per 0.01 increase in peripheral corneal thickness) at baseline were associated with an increased 14-year risk of progression from PACS to PAC. As for AS-OCT measurements, smaller light-room trabecular-iris space area (TISA) at 500 µm from the scleral spur (OR, 0.86 [95% CI, 0.77-0.96] per 0.01-mm2 increase), smaller light-room angle recess area (ARA) at 750 µm from the scleral spur (OR, 0.93 [95% CI, 0.88-0.98] per 0.01-mm2 increase), and smaller dark-room TISA at 500 µm (OR, 0.89 [95% CI, 0.80-0.98] per 0.01-mm2 increase) at baseline were identified as predictors for the 14-year risk of progression. The prediction models based on IOP and central and limbal ACDs showed moderate performance (area under the receiver operating characteristic curve, 0.69; 95% CI, 0.63-0.75) in predicting progression from PACS to PAC, and inclusion of AS-OCT metrics did not improve the model's performance. Conclusions and Relevance: This cohort study suggests that higher IOP, shallower central and limbal ACDs, and smaller TISA at 500 µm and light-room ARA at 750 µm may serve as baseline predictors for progression to PAC in PACS eyes. Evaluating these factors can aid in customizing PACS management.

Metabolic fingerprinting on retinal pigment epithelium thickness for individualized risk stratification of type 2 diabetes mellitus.

The retina is an important target organ of diabetes mellitus, with increasing evidence from patients and animal models suggesting that retinal pigment epithelium (RPE) may serve as an early marker for diabetes-related damages. However, their longitudinal relationship and the biological underpinnings remain less well understood. Here, we demonstrate that reduced in vivo measurements of RPE thickness (RPET) represents a significant risk factor for future type 2 diabetes mellitus (T2DM) and its microvascular phenotypes. After performing systematic analyses of circulating plasma metabolites using two complementary approaches, we identify a wide range of RPET metabolic fingerprints that are independently associated with reduced RPET. These fingerprints hold their potential to improve predictability and clinical utility for stratifying future T2DM and related microvascular phenotypes beyond traditional clinical indicators, providing insights into the promising role of retinas as a window to systemic health.

Association of central obesity with retinal neurodegeneration: Cross-sectional and longitudinal evidence from two countries.

OBJECTIVE: This study aimed to evaluate the association of central obesity with retinal neurodegeneration. METHODS: Databases from the UK Biobank study and the Chinese Ocular Imaging Project (COIP) were included for cross-sectional and longitudinal analyses, respectively. Retinal ganglion cell-inner plexiform layer thickness (GCIPLT) measured by optical coherence tomography (OCT) was used as a retinal indicator of neurodegeneration. All subjects were divided into six obesity phenotypes according to BMI (normal, overweight, obesity) and waist to hip ratio (WHR; normal, high). Multivariable linear regression models were fitted to investigate the association of obesity phenotypes with GCIPLT. RESULTS: A total of 22,827 and 2082 individuals from UK Biobank (mean age: 55.06 [SD 8.27] years, women: 53.2%) and COIP (mean age: 63.02 [SD 8.35 years], women: 61.9%) were included, respectively. Cross-sectional analysis showed GCIPLT was significantly thinner in normal BMI/high WHR individuals compared with normal BMI/normal WHR individuals (ß = -0.33 µm, 95% CI = -0.61, -0.04, p = 0.045). But thinner GCIPLT was not observed in individuals with obesity/normal WHR. After 2-year follow-up in COIP, normal BMI/high WHR was associated with accelerated GCIPLT thinning (ß = -0.28 µm/y, 95% CI = -0.45, -0.10, p = 0.02), whereas obesity/normal WHR was not. CONCLUSIONS: Even with normal weight, central obesity was associated with accelerated GCIPLT thinning cross-sectionally and longitudinally.

The Mediterranean Diet and Age-Related Eye Diseases: A Systematic Review.

The Mediterranean diet (MD) is a healthy diet pattern that can prevent chronic age-related diseases, especially age-related eye diseases (AREDs) including cataract, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR) and dry eye syndrome (DES). In this study, we systematically reviewed studies in the literature that had reported associations between adherence to the MD and the five above-mentioned AREDs. Randomized controlled trials as well as prospective and retrospective observational studies were included; 1164 studies were identified, of which 1, 2, 9, 2 and 4 studies met our eligibility criteria for cataract, glaucoma, AMD, DR, and DES, respectively. According to these studies, higher MD adherence was associated with reduced risks of incident DR, incident AMD and progression to late AMD, but whether early and neovascular AMD could be alleviated remained to be debated. The results regarding the effects of the MD on DES were mixed, with three studies reporting an associations between MD and decreased severity or incidence of DES, whereas one study reported the opposite. No significant associations were observed between the MD and cataract or glaucoma. Generally, convincing evidence suggested a protective effect of the MD against AMD and DR. However, the evidence for cataract, glaucoma, and DES was less conclusive, and high-quality studies are needed for comprehensive evaluations of the potential benefits of MD on these eye diseases.

Segmentation Errors and Off-Center Artifacts in SS-OCT: Insight from a Population-Based Imaging Study.

PURPOSE: To evaluate the frequency and associated factors of artifacts in swept-source optical coherence tomography (SS-OCT) imaging. METHODS: This was a population-based cross-sectional study. Individuals aged 35 years or older, residing in the Yuexiu district of Guangzhou, China, were recruited by random cluster sampling. Nearly half of the participants were randomly selected for SS-OCT imaging centered on the optic nerve head. Six types of artifacts in the peripapillary choroidal layer and retinal nerve fiber layer (RNFL) were graded and identified. Univariate and multivariate logistic regression analyses were used to investigate the association between the presence of artifacts and clinical characteristics. RESULTS: Out of the 616 eligible individuals who underwent SS-OCT imaging, 18.3% and 13.6% of subjects exhibited at least one artifact in peripapillary RNFL (pRNFL) and peripapillary choroidal thickness (pCT) measurements, respectively, with posterior segmentation error and off-center artifact ranked as the most common artifacts. The presence of artifacts was significantly associated with age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06; p = .003), refractive error (OR, 0.80; 95% CI, 0.71-0.89; p < .001), and signal strength (OR, 0.95; 95% CI, 0.90-0.997; p = .039) in pRNFL thickness measurement. Similarly, the presence of artifacts in pCT measurement was significantly associated with age (OR, 1.05; 95% CI, 1.03-1.08; p < .001), and refractive error (OR, 0.76; 95% CI, 0.68-0.86; p < .001). CONCLUSION: Nearly one-fifth of the eyes were noted with at least one artifact in the population-scale SS-OCT study. Age was a risk factor for the presence of artifacts and should be considered in clinical settings.

Analysis of Plasma Metabolic Profile on Ganglion Cell-Inner Plexiform Layer Thickness With Mortality and Common Diseases.

Importance: The neural retina is considered a unique window to systemic health, but its biological link with systemic health remains unknown. Objective: To investigate the independent associations of retinal ganglion cell-inner plexiform layer thickness (GCIPLT) metabolic profiles with rates of mortality and morbidity of common diseases. Design, Setting, and Participants: This cohort study evaluated UK Biobank participants enrolled between 2006 and 2010, and prospectively followed them up for multidisease diagnosis and mortality. Additional participants from the Guangzhou Diabetes Eye Study (GDES) underwent optical coherence tomography scanning and metabolomic profiling and were included for validation. Main Outcomes and Measures: Systematic analysis of circulating plasma metabolites to identify GCIPLT metabolic profiles; prospective associations of these profiles with mortality and morbidity of 6 common diseases with their incremental discriminative value and clinical utility. Results: Among 93 838 community-based participants (51 182 [54.5%] women), the mean (SD) age was 56.7 (8.1) years and mean (SD) follow-up was 12.3 (0.8) years. Of 249 metabolic metrics, 37 were independently associated with GCIPLT, including 8 positive and 29 negative associations, and most were associated with the rates of future mortality and common diseases. These metabolic profiles significantly improved the models for discriminating type 2 diabetes over clinical indicators (C statistic: 0.862; 95% CI, 0.852-0.872 vs clinical indicators only, 0.803; 95% CI, 0.792-0.814; P < .001), myocardial infarction (0.792; 95% CI, 0.775-0.808 vs 0.768; 95% CI, 0.751-0.786; P < .001), heart failure (0.803; 95% CI, 0.786-0.820 vs 0.790; 95% CI, 0.773-0.807; P < .001), stroke (0.739; 95% CI, 0.714-0.764 vs 0.719; 95% CI, 0.693-0.745; P < .001), all-cause mortality (0.747; 95% CI, 0.734-0.760 vs 0.724; 95% CI, 0.711-0.738; P < .001), and cardiovascular disease mortality (0.790; 95% CI, 0.767-0.812 vs 0.763; 95% CI, 0.739-0.788; P < .001). Additionally, the potential of GCIPLT metabolic profiles for risk stratification of cardiovascular diseases were further confirmed in the GDES cohort using a different metabolomic approach. Conclusions and Relevance: In this prospective study of multinational participants, GCIPLT-associated metabolites demonstrated the potential to inform mortality and morbidity risks. Incorporating information on these profiles may facilitate individualized risk stratification for these health outcomes.

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.

Fourteen-Year Outcome of Angle-Closure Prevention with Laser Iridotomy in the Zhongshan Angle-Closure Prevention Study: Extended Follow-up of a Randomized Controlled Trial.

PURPOSE: This study aimed to evaluate the efficacy of laser peripheral iridotomy (LPI) prophylaxis for patients with primary angle-closure suspect (PACS) after 14 years and to identify risk factors for the conversion from PACS to primary angle closure (PAC). DESIGN: Extended follow-up of the Zhongshan Angle-Closure Prevention Study. PARTICIPANTS: Eight hundred eighty-nine Chinese patients 50 to 70 years of age with bilateral PACS. METHODS: Each patient received LPI in 1 randomly selected eye, with the fellow untreated eye serving as a control. Because the risk of glaucoma was low and acute angle closure (AAC) occurred only rarely, the follow-up was extended to 14 years despite substantial benefits of LPI reported after the 6-year visit. MAIN OUTCOME MEASURES: Incidence of PAC, a composite end point including peripheral anterior synechiae, intraocular pressure (IOP) of > 24 mmHg, or AAC. RESULTS: During the 14 years, 390 LPI-treated eyes and 388 control eyes were lost to follow-up. A total of 33 LPI-treated eyes and 105 control eyes reached primary end points (P < 0.01). Within them, 1 LPI-treated eye and 5 control eyes progressed to AAC. Primary angle-closure glaucoma was found in 2 LPI-treated eyes and 4 control eyes. The hazard ratio for progression to PAC was 0.31 (95% confidence interval, 0.21-0.46) in LPI-treated eyes compared with control eyes. At the 14-year visit, LPI-treated eyes showed more severe nuclear cataract, higher IOP, and larger angle width and limbal anterior chamber depth (LACD) than control eyes. Higher IOP, shallower LACD, and greater central anterior chamber depth (CACD) were associated with an increased risk of end points developing in control eyes. In the treated group, eyes with higher IOP, shallower LACD, or less IOP elevation after the darkroom prone provocative test (DRPPT) were more likely to demonstrate PAC after LPI. CONCLUIONS: Despite a two-third decrease in PAC occurrence after LPI, the cumulative risk of progression was relatively low in the community-based PACS population over 14 years. Apart from IOP, IOP elevation after DRPPT, CACD, and LACD, more risk factors are needed to achieve precise prediction of PAC occurrence and to guide clinical practice. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

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.

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).

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.

Longitudinal Changes and Predictive Value of Choroidal Thickness for Myopia Control after Repeated Low-Level Red-Light Therapy.

PURPOSE: To evaluate longitudinal changes in macular choroidal thickness (mCT) in myopic children treated for 1 year with repeated low-level red-light (RLRL) therapy and their predictive value for treatment efficacy on myopia control. DESIGN: A secondary analysis of data from a multicenter, randomized controlled trial (RCT; NCT04073238). PARTICIPANTS: Myopic children aged 8-13 years who participated in the RCT at 2 of 5 sites where mCT measurements were available. METHODS: Repeated low-level red-light therapy was delivered using a home-use desktop light device that emitted red-light at 650 nm. Choroidal thickness was measured by SS-OCT at baseline and 1-, 3-, 6-, and 12-month follow-ups. Visual acuity, axial length (AL), cycloplegic spherical equivalent refraction (SER), and treatment compliance were measured. MAIN OUTCOME MEASURES: Changes in mCT at 1, 3, 6, and 12 months relative to baseline, and their associations with myopia control. RESULTS: A total of 120 children were included in the analysis (RLRL group: n = 60; single-vision spectacle [SVS] group: n = 60). Baseline characteristics were well balanced between the 2 groups. In the RLRL group, changes in mCT from baseline remained positive over 1 year, with a maximal increase of 14.755 µm at 1 month and gradually decreasing from 5.286 µm at 3 months to 1.543 µm at 6 months, finally reaching 9.089 µm at 12 months. In the SVS group, mCT thinning was observed, with changes from baseline of -1.111, -8.212, -10.190, and -10.407 µm at 1, 3, 6, and 12 months, respectively. Satisfactory myopia control was defined as annual progression rates of less than 0, 0.05, or 0.10 mm for AL and less than 0, 0.25, or 0.50 diopters for SER. Models that included mCT changes at 3 months alone had acceptable predictive discrimination of satisfactory myopia control over 12 months, with areas under the curve of 0.710-0.786. The predictive performance of the models did not significantly improve after adding age, gender, and baseline AL or SER. CONCLUSIONS: This analysis from a multicenter RCT found RLRL induced sustained choroidal thickening over the full course of treatment. Macular choroidal thickness changes at 3 months alone can predict 12-month myopia control efficacy with reasonable accuracy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Association between statin use and the risks of glaucoma in Australia: a 10-year cohort study.

SYNOPSIS: In a cohort of middle-aged and elderly Australians, we found that long-term statin use was associated with a higher risk of glaucoma onset. As to subtypes of statins, the increased risk was only found in rosuvastatin users. PURPOSE: To investigate the relationship between statin use and glaucoma onset in a 10-year longitudinal study. METHODS: This nested case-control study was based on data from a large-scale cohort of Australians aged over 45 years old. Medication exposure was identified by claims records from the Pharmaceutical Benefits Scheme during the follow-up period (2009-2016). The onset of glaucoma was defined as the people with at least three claims of antiglaucoma medications. Controls matched by age, gender and cardiovascular diseases were selected from participants without prescription of antiglaucoma medications. A conditional logistic regression model was used to assess the association between statin use and glaucoma onset. RESULTS: The proportion of statin users was higher in the case group (40.5%) than that in the control group (38.4%). After adjusting for baseline characteristics and longitudinal claims records, statin use was not associated with glaucoma onset (OR 1.04, 95% CI 0.97 to 1.11). However, an increased risk of glaucoma onset was observed in participants with a longer duration of statin use (>3 years vs <1 year: OR 1.12, 95% CI 1.04 to 1.21). With respect to specific types of statins, participants taking rosuvastatin were more likely to suffer from glaucoma (OR 1.11, 95%CI 1.01 to 1.22). The use of other statins was not significantly associated with glaucoma onset. CONCLUSIONS: Long-term statin use was found to be associated with a higher risk of glaucoma onset in this study. Regarding specific types of statins, the increased risk of glaucoma onset was only observed in users of rosuvastatin.

Daily Patterns of Accelerometer-Measured Movement Behaviors in Glaucoma Patients: Insights From UK Biobank Participants.

PURPOSE: The purpose of this study is to compare daily patterns of accelerometer-measured movement behaviors between glaucoma patients and those without glaucoma. METHODS: From 2013 to 2015, 106,053 UK Biobank participants took part in a 7-day accelerometer test. Based on established algorithms, continuous accelerometer data were classified into 4 movement behaviors: moderate to vigorous physical activity (MVPA), light physical activity, sedentary behaviors, and sleep. Glaucoma and other covariates were defined according to baseline assessments and inpatient diagnosis records. Negative binomial regression models were used to compare daily patterns of movement behaviors between glaucoma patients and those without glaucoma. RESULTS: Accelerometer data from 1262 glaucoma patients and 81,551 participants without glaucoma were included. Compared with participants without glaucoma, glaucoma patients spent 4.7% less time on MVPA in multivariable models [mean=28.3 vs 31.4 min/d; incidence-rate ratio (IRR) 0.953, 95% confidence interval (CI): 0.910-0.998; P=0.044], which was mainly attributed to the decreased MVPA time during 18:00-23:59 (IRR=0.863, Bonferroni-corrected 95% CI: 0.768-0.970; P=0.002). Subgroup analyses indicated that compared with those with normal body mass index, the decreased MVPA time was more pronounced in participants with overweight and obesity (IRR=0.912, Bonferroni-corrected 95% CI: 0.851-0.978; P for interaction=0.007). No significant association was found between glaucoma and time spent on other movement behaviors including light physical activity, sedentary behaviors, and sleep. CONCLUSIONS: Daily patterns of movement behaviors were significantly changed in glaucoma patients. Compared with those without glaucoma, glaucoma patients spent less time on MVPA, especially in the evening.

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.

Use of antihypertensive medications and the risk of glaucoma onset: Findings from the 45 and Up Study.

BACKGROUND: Abnormal blood pressure is a potential risk factor for glaucoma. However, the role of antihypertensive medications on glaucoma pathogenesis is controversial. This study aims to investigate the association between the use of antihypertensive medications and glaucoma onset. METHODS: This nested case-control study, based on a large-scale longitudinal cohort in Australia, retrieved participants' claims records on drugs and Medicare services from national health databases. Participants with three or more claim records of anti-glaucoma medications from 2009 to 2016 were classified as glaucoma patients; those with none were classified as controls. Claim records of antihypertensive medications were identified within the 5 years before glaucoma onset and contemporary periods in matched controls without glaucoma. The association between the use of antihypertensive medications and glaucoma onset was assessed by multivariable logistic regression models. RESULTS: A total of 6748 cases and 13 496 controls were analysed. Compared with controls, the proportion of users of antihypertensive medications was slightly higher in glaucoma patients (46.9% vs. 46.0%, p > 0.05). After adjustments for demographics, health-related factors and medical history, the association between the use of antihypertensive medications and glaucoma onset was nonsignificant (OR 0.95, 95% CI = 0.89-1.02). As for specific subtypes, only beta-blocking agents (BBA) (OR 0.82, 95% CI = 0.75-0.90) and diuretics (OR 0.85, 95% CI = 0.77-0.95) were significantly associated with reduced risks of glaucoma onset. CONCLUSIONS: This study indicated that the use of antihypertensive medications was not associated with glaucoma onset. Decreased risks of glaucoma onset in users of BBA and diuretics require further validation.

Associations of statin use with the onset and progression of open-angle glaucoma: A systematic review and meta-analysis.

Background: Statins, the first-line therapy for hyperlipidemia, have received considerable attention as candidates for glaucoma treatments given its neuroprotective effects. In this systematic review and meta-analysis, we intended to assess the association of statin use with the onset and progression of open-angle glaucoma (OAG). Methods: Databases including PubMed, Embase and Web of Science Core Collection were searched for longitudinal studies reporting the association between statin use and OAG onset or progression on Feb 3, 2021. A meta-analysis was performed for the association between statin use and OAG onset. Relative risks (RRs) with 95% confidential intervals (CIs) were retrieved from included studies and pooled using random-effects models. Potential risks of bias were evaluated by the Newcastle-Ottawa Quality Assessment Scale for all eligible studies. This study had been registered on PROSPERO (CRD 42021232172). Findings: 515,788 participants (mean age 68.7 years, 62.3% female) from ten studies were included in the systematic review of the association between statin use and OAG onset, and 26,347 OAG patients (mean age 67.3 years, 52.2% female) from seven studies were included for the association between statin use and OAG progression. Potential risks of bias were detected in 12 studies, which were mainly attributed to selection and confounding bias. In addition, 515,600 participants from eight studies were included in the meta-analysis which collectively showed that statin use was associated with a reduced risk of OAG onset (Pooled RR: 0.95; 95%CI: 0.93-0.98; I2=0.199;). No significant heterogeneity or publication bias was found for studies included in the meta-analysis. There were inconsistent evidences for the association between statin use and OAG progression. Interpretation: Statin use is associated with a slightly lower risk of OAG onset based on existing evidences from longitudinal observational studies, the association between statin use and OAG progression remains inconclusive. The included evidences were typically weak due to poor study design and under-powered studies. Current findings should be interpreted cautiously and still need to be validated in further research. Funding: The National Key R&D Program of China (2018YFC0116500), Science and Technology Planning Project of Guangdong Province (2013B20400003), the China Postdoctoral Science Foundation (2019TQ0365), the National Natural Science Foundation of China (82000901 and 82101171).