Myopia Control Effect of Repeated Low-Level Red-Light Therapy Combined with Orthokeratology: A Multicenter Randomized Controlled Trial.

PURPOSE: To investigate the efficacy and safety of repeated low-level red-light(RLRL) therapy combined with orthokeratology(Ortho-k) among the children who, despite undergoing Ortho-k treatment, exhibited an axial elongation of at least 0.50mm over 1 year. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial (ClinicaTrials.gov,NCT04722874). PARTICIPANTS: Eligible children were aged 8-13 years with a cycloplegic spherical equivalent refraction of -1.00 to -5.00 diopters in the initial Ortho-k fitting examination and had annual axial length (AL) elongation ≥ 0.50 mm despite undergoing Ortho-k for 1 year. A total of 48 children were enrolled from March 2021 to January 2022, and the final follow-up was completed in March 2023. METHODS: Children were randomly assigned to the RLRL combined with Ortho-k(RCO) or the Ortho-k group in a 2:1 ratio. The Ortho-k group wore Ortho-k at least 8 hours per night, while the RCO group received daily RLRL therapy twice a day for 3 minutes in addition to Ortho-k wearing. MAIN OUTCOME MEASURES: The primary outcome was AL change measured at 12 months relative to baseline. The primary analysis was conducted in children who received the assigned intervention and completed at least 1 post-randomization follow-up using the modified intention-to-treat principle. RESULTS: A total of 47(97.9%) children were included in the analysis (30 in the RCO group and 17 in the Ortho-k group). The mean axial elongation rate before the trial was 0.60mm/year in the RCO group and 0.61mm/year in the Ortho-k group. After 12 months following the intended intervention, the adjusted mean AL changes were -0.02mm(95% CI, -0.08 to +0.03 mm) in the RCO group and 0.27mm(0.19-0.34 mm) in the Ortho-k group. The adjusted mean difference in AL change was -0.29mm(-0.44 to -0.14mm) between the RCO and Ortho-k groups. The percentage of children achieving an uncorrected visual acuity greater than 20/25 was similar in the RCO (64.3%) and Ortho-k (65.5%) groups (Chi2 test, P=0.937). CONCLUSIONS: Combining RLRL therapy with Ortho-k may offer a promising approach to optimize axial elongation control among myopic children. This approach also potentially allows children to achieve satisfactory visual acuity, reducing the daytime dependence on corrective eyewear.

Breaking Continuously Packed Bimetallic Sites to Singly Dispersed on Nonmetallic Support for Efficient Hydrogen Production.

We have synthesized Pt1Zn3/ZnO, also termed 0.01 wt %Pt/ZnO-O2-H2, as a catalyst containing singly dispersed single-atom bimetallic sites, also called a catalyst of singly dispersed bimetallic sites or a catalyst of isolated single-atom bimetallic sites. Its catalytic activity in partial oxidation of methanol to hydrogen at 290 °C is found to be 2-3 orders of magnitude higher than that of Pt-Zn bimetallic nanoparticles supported on ZnO, 5.0 wt %Pt/ZnO-N2-H2. Selectivity for H2 on Pt1Zn3/ZnO reaches 96%-100% at 290-330 °C, arising from the uniform coordination environment of single-atom Pt1 in singly dispersed single-atom bimetallic sites, Pt1Zn3 on 0.01 wt %Pt/ZnO-O2-H2, which is sharply different from various coordination environments of Pt atoms in coexisting PtxZny (x ≥ 0, y ≥ 0) sites on Pt-Zn bimetallic nanoparticles. Computational simulations attribute the extraordinary catalytic performance of Pt1Zn3/ZnO to the stronger adsorption of methanol and the lower activation barriers in O-H dissociation of CH3OH, C-H dissociations of CH2O to CO, and coupling of intermediate CO with atomic oxygen to form CO2 on Pt1Zn3/ZnO as compared to those on Pt-Zn bimetallic nanoparticles. It demonstrates that anchoring uniform, isolated single-atom bimetallic sites, also called singly dispersed bimetallic sites on a nonmetallic support can create new catalysts for certain types of reactions with much higher activity and selectivity in contrast to bimetallic nanoparticle catalysts with coexisting, various metallic sites MxAy (x ≥ 0, y ≥ 0). As these single-atom bimetallic sites are cationic and anchored on a nonmetallic support, the catalyst of singly dispersed single-atom bimetallic sites is different from a single-atom alloy nanoparticle catalyst. The critical role of the 0.01 wt %Pt in the extraordinary catalytic performance calls on fundamental studies of the profound role of a trace amount of a metal in heterogeneous catalysis.

Real-world application of a smartphone-based visual acuity test (WHOeyes) with automatic distance calibration.

BACKGROUND: To develop and assess the usability of a smartphone-based visual acuity (VA) test with an automatic distance calibration (ADC) function, the iOS version of WHOeyes. METHODS: The WHOeyes was an upgraded version with a distinct feature of ADC of an existing validated VA testing app called V@home. Three groups of Chinese participants with different ages (≤20, 20-40, >40 years) were recruited for distance and near VA testing using both an Early Treatment Diabetic Retinopathy Study (ETDRS) chart and the WHOeyes. The ADC function would determine the testing distance. Infrared rangefinder was used to determine the testing distance for the ETDRS, and actual testing distance for the WHOeyes. A questionnaire-based interview was administered to assess the satisfaction. RESULTS: The actual testing distance determined by the WHOeyes ADC showed an overall good agreement with the desired testing distance in all three age groups (p>0.50). Regarding the distance and near VA testing, the accuracy of WHOeyes was equivalent to ETDRS. The mean difference between the WHOeyes and ETDRS ranged from -0.084 to 0.012 logMAR, and the quadratic weighted kappa (QWK) values were >0.75 across all groups. The test-retest reliability of WHOeyes was high for both near and distance VA, with a mean difference ranging from -0.040 to 0.004 logMAR and QWK all >0.85. The questionnaire revealed an excellent user experience and acceptance of WHOeyes. CONCLUSIONS: WHOeyes could provide accurate measurement of the testing distance as well as the distance and near VA when compared to the gold standard ETDRS chart.

Deep neural network-estimated age using optical coherence tomography predicts mortality.

The concept of biological age has emerged as a measurement that reflects physiological and functional decline with ageing. Here we aimed to develop a deep neural network (DNN) model that predicts biological age from optical coherence tomography (OCT). A total of 84,753 high-quality OCT images from 53,159 individuals in the UK Biobank were included, among which 12,631 3D-OCT images from 8,541 participants without any reported medical conditions at baseline were used to develop an age prediction model. For the remaining 44,618 participants, OCT age gap, the difference between the OCT-predicted age and chronological age, was calculated for each participant. Cox regression models assessed the association between OCT age gap and mortality. The DNN model predicted age with a mean absolute error of 3.27 years and showed a strong correlation of 0.85 with chronological age. After a median follow-up of 11.0 years (IQR 10.9-11.1 years), 2,429 deaths (5.44%) were recorded. For each 5-year increase in OCT age gap, there was an 8% increased mortality risk (hazard ratio [HR] = 1.08, CI:1.02-1.13, P = 0.004). Compared with an OCT age gap within ± 4 years, OCT age gap less than minus 4 years was associated with a 16% decreased mortality risk (HR = 0.84, CI: 0.75-0.94, P = 0.002) and OCT age gap more than 4 years showed an 18% increased risk of death incidence (HR = 1.18, CI: 1.02-1.37, P = 0.026). OCT imaging could serve as an ageing biomarker to predict biological age with high accuracy and the OCT age gap, defined as the difference between the OCT-predicted age and chronological age, can be used as a marker of the risk of mortality.

Axial Elongation Trajectories in Chinese Children and Adults With High Myopia.

Importance: Understanding the long-term axial elongation trajectory in high myopia is important to prevent blindness. Objective: To evaluate axial elongation trajectories and related visual outcomes in children and adults with high myopia. Design, Setting, and Participants: In this cohort study, participants in the Zhongshan Ophthalmic Centre-Brien Holden Vision Institute high myopia cohort were followed up every other year for 8 years. Participants with axial length measurements at baseline (2011 or 2012) and at least 1 follow-up visit were included. Participants were grouped according to baseline age as children and adolescents (7 to <18 years), young adults (18 to <40 years), and older adults (≥40 to 70 years). Data were analyzed from November 1, 2022, to June 1, 2023. Exposure: High myopia (spherical power ≤-6.00 diopters). Main Outcomes and Measures: Longitudinal axial elongation trajectories were identified by cluster analysis. Axial elongation rates were calculated by linear mixed-effects models. A 2-sided P < .05 was defined as statistically significant. Results: A total of 793 participants (median [range] age, 17.8 [6.8-69.7] years; 418 females [52.7%]) and 1586 eyes were included in the analyses. Mean axial elongation rates were 0.46 mm/y (95% CI, 0.44-0.48 mm/y) for children and adolescents, 0.07 mm/y (95% CI, 0.06-0.09 mm/y) for young adults, and 0.13 mm/y (95% CI, 0.07-0.19 mm/y) for older adults. Cluster analysis identified 3 axial elongation trajectories, with the stable, moderate, and rapid progression trajectories having mean axial elongation rates of 0.02 mm/y (95% CI, 0.01-0.02 mm/y), 0.12 mm/y (95% CI, 0.11-0.13 mm/y), and 0.38 mm/y (95% CI, 0.35-0.42 mm/y), respectively. At 8 years of follow-up, compared with the stable progression trajectory, the rapid progression trajectory was associated with a 6.92 times higher risk of developing pathological myopic macular degeneration (defined as diffuse or patchy chorioretinal atrophy or macular atrophy; odds ratio, 6.92 [95% CI, 1.07-44.60]; P = .04), and it was associated with a 0.032 logMAR decrease in best-corrected visual acuity (ß = 0.032 [95% CI, 0.001-0.063]; P = .04). Conclusions and Relevance: The findings of this 8-year follow-up study suggest that axial length in high myopia continues to increase from childhood to late adulthood following 3 distinct trajectories. At 8 years of follow-up, the rapid progression trajectory was associated with a higher risk of developing pathological myopic macular degeneration and poorer best-corrected visual acuity compared with the stable progression trajectory. These distinct axial elongation trajectories could prove valuable for early identification and intervention for high-risk individuals.

Serum cystatin C for risk stratification of prediabetes and diabetes populations.

BACKGROUND: The association between serum cystatin C level and vascular outcomes has not been fully elucidated in diabetes and is unclear in prediabetes. We aim to evaluate whether cystatin C level predicts future risk for mortality and vascular outcomes in prediabetes and diabetes. METHODS: A total of 85,371 participants with prediabetes and diabetes, and available baseline cystatin C in the UK biobank were included with a 14-year follow-up. Cox hazards models were used to calculate the associations between cystatin C level, mortality (all-cause, cause-specfic mortality) and vascular outcomes (myocardial infarction [MI], stroke, end-stage renal disease [ESRD] and diabetic retinopathy [DR]). The 1136 diabetes subjects in Guangzhou Diabetic Eye Study (GDES) were included for examing the impact of cystatin C on in vivo retinal degeneration and microvascular changes by using SS-OCT and OCTA. RESULTS: The highest cystatin C quartile had increased risks of all-cause (hazard ratio [HR], 2.02; 95% confidence interval [CI] 1.86-2.19), cardiovascular (HR, 2.29; 95% CI 1.97-2.67), cancer (HR, 1.86; 95% CI 1.65-2.10) and other-cause mortality (HR, 2.24; 95% CI 1.90-2.64), MI (HR, 1.40; 95% CI 1.26-1.55), stroke (HR, 1.88; 95% CI, 1.57-2.26), ESRD (HR, 7.33; 95% CI, 5.02-10.71), DR (HR, 1.17; 95% CI 1.03-1.32) than those in the lowest quartile. Adding cystatin C to the conventional model improved C-statistic for all-cause (0.699-0.724), cardiovascular (0.762-0.789), cancer (0.661-0.674) and other-cause mortality (0.675-0.715), MI (0.748-0.750), stroke (0.712-0.718), and ESRD (0.808-0.827). The GDES analysis identified a strong association between increased cystatin C levels and diminished retinal neural layers, as well as microvascular rarefaction in both macular and optic disc regions (all P < 0.05). CONCLUSIONS: Serum cystatin C refines the risk stratification for mortality and vascular outcomes among patients with prediabetes or diabetes.

Developments and challenges in neoadjuvant therapy for locally advanced pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) remains a significant public health challenge and is currently the fourth leading cause of cancer-related mortality in developed countries. Despite advances in cancer treatment, the 5-year survival rate for patients with PDAC remains less than 5%. In recent years, neoadjuvant therapy (NAT) has emerged as a promising treatment option for many cancer types, including locally advanced PDAC, with the potential to improve patient outcomes. To analyze the role of NAT in the setting of locally advanced PDAC over the past decade, a systematic literature search was conducted using PubMed and Web of Science. The results suggest that NAT may reduce the local mass size, promote tumor downstaging, and increase the likelihood of resection. These findings are supported by the latest evidence-based medical literature and the clinical experience of our center. Despite the potential benefits of NAT, there are still challenges that need to be addressed. One such challenge is the lack of consensus on the optimal timing and duration of NAT. Improved criteria for patient selection are needed to further identify PDAC patients likely to respond to NAT. In conclusion, NAT has emerged as a promising treatment option for locally advanced PDAC. However, further research is needed to optimize its use and to better understand the role of NAT in the management of this challenging disease. With continued advances in cancer treatment, there is hope of improving the outcomes of patients with PDAC in the future.

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.

Case report and literature review: Isolated HCC- recurrence in gallbladder after curative resection.

Background: Liver resection (LR) is considered the mainstay treatment for eligible patients with hepatocellular carcinoma (HCC) and provides a 5-year overall survival (OS) of 60%-80%. However, the recurrence rate within five years after LR remains high, ranging from 40% to 70%. Recurrence in gallbladder after liver resection is extremely rare. Here, we present a case of isolated recurrence in gallbladder after curative resection of HCC and review the relevant literature. No similar cases have been reported before. Case presentation: A 55-year-old male patient was diagnosed with HCC in 2009 and subsequently underwent a right posterior sectionectomy of the liver. In 2015, the patient underwent liver tumor radiofrequency ablation and three transarterial chemoembolization (TACE) procedures in succession for HCC recurrence. In 2019, a gallbladder lesion was detected by computed tomography (CT) without perceivable intrahepatic focus. We performed an en bloc resection of the gallbladder and hepatic segment IVb. The pathological biopsy suggested that the gallbladder tumor was moderately differentiated HCC. The patient survived more than 3 years in good condition, and there were no signs of tumor recurrence. Conclusions: In patients with isolated gallbladder metastasis, if the lesion can be resected en bloc without remnants, surgery should be the preferred option. Both postoperative molecularly targeted drugs and immunotherapy are expected to improve the long-term prognosis.

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.

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

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

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

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

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

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

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.

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.

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.

Rates of Choroidal and Neurodegenerative Changes Over Time in Diabetic Patients Without Retinopathy: A 3-Year Prospective Study.

PURPOSE: To evaluate the longitudinal changes of retinal neurodegeneration and choroidal thickness in diabetic patients with and without diabetic retinopathy (DR). DESIGN: Prospective observational cohort study. METHODS: This prospective observational cohort study recruited type 2 diabetic patients from a community registry in Guangzhou. All participants underwent annual ocular examinations via swept-source optical coherence tomography that obtained choroid thickness (CT), retinal thickness (RT), and ganglion cell-inner plexiform layer (GC-IPL) thickness. The changes in GC-IPL, CT, and RT between patients who developed incident DR (IDR) or remained non-DR (NDR) were compared during a 3-year follow-up. RESULTS: Among 924 patients, 159 (17.2%) patients developed IDR within the 3-year follow-up. A reduction in GC-IPL, RT, and CT was observed in NDR and IDR; however, CT thinning in patients with IDR was significantly accelerated, with an average CT reduction of -6.98 (95% CI: -8.26, -5.71) µm/y in patients with IDR and -3.98 (95% CI: -4.60, -3.36) µm/y in NDR patients (P < .001). Reductions in average GC-IPL thickness over 3 years were -0.97 (95% CI: -1.24, -0.70) µm/y in patients with IDR and -0.76 (95% CI: -0.82, -0.70) µm/y in NDR patients (P = .025). After adjusting for confounding factors, the average CT and GC-IPL thinning were significantly faster in patients with IDR compared with those who remained NDR by 2.09 µm/y (95% CI: 1.01, 3.16; P = .004) and -0.29 µm/y (95% CI: -0.49, -0.09; P = .004), respectively. The RT in the IDR group increased, whereas the RT in the NDR group decreased over time, with the adjusted difference of 2.09 µm/y (95% CI: 1.01, 3.16; P < .001) for central field RT. CONCLUSIONS: The rate of retinal neurodegeneration and CT thinning were significantly different between the eyes that developed IDR and remained NDR during the 3-year follow-up, but both groups observed thickness reduction. This indicates that GC-IPL and CTs may decrease before the clinical manifestations of DR.

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.

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.

PROGRESSIVE PERIPAPILLARY CHOROID THINNING AND RETINAL NEURODEGENERATION IN PATIENTS WITH DIABETES: A 3-Year Cohort Study.

PURPOSE: To investigate longitudinal changes in peripapillary choroidal thickness (pCT) and retinal nerve fiber thickness (pRNFLT) in patients with Type 2 diabetes mellitus. METHODS: This was a prospective observational cohort study. Patients with Type 2 diabetes mellitus without diabetic retinopathy (DR) at baseline were recruited, followed up for three years, and further divided into an incident DR group and a non-DR group according to the outcome. The pCT and pRNFLT were measured through swept-source optical coherence tomography at 1-year interval, and the mean rates of pCT and pRNFLT thinning were compared between the DR groups. RESULTS: A total of 682 patients (682 eyes) were included in the final analysis. After 3-years follow-up, 122 (17.89%) developed DR. Both pCT and pRNFLT progressively thinned (-2.37 [-2.80 to -1.95] µm/year; -0.40 [-0.55 to -0.25] µm/year, respectively, P < 0.05) and accelerated thinning was observed in the incident DR group. The rates of pCT thinning (-3.92 [-4.96 to -2.88] µm/year, -2.03 [-2.49 to -1.57] µm/year, respectively) and pRNFLT loss (-1.03 [-1.31 to -0.76] µm/year, -0.26 [-0.43 to -0.09] µm/year, respectively) in the incident DR group were 1.93 and 3.96 times faster than those in the non-DR group, respectively. In addition, pCT and pRNFLT thinning were negatively related in Type 2 diabetes mellitus population, and faster pCT thinning indicated slower pRNFLT loss. CONCLUSION: Patients with Type 2 diabetes mellitus were at a higher risk of developing DR when accelerated pCT and pRNFLT thinning were present, indicating that heavier choroidal damage and retinal neurodegeneration precede clinical DR. The pCT and pRNFLT have the potential to serve as novel sensitive biomarkers of preclinical and early DR.