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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.A secondary analysis of data from a multicenter, randomized controlled trial (RCT; NCT04073238).Myopic children aged 8-13 years who participated in the RCT at 2 of 5 sites where mCT measurements were available.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.Changes in mCT at 1, 3, 6, and 12 months relative to baseline, and their associations with myopia control.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.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.Proprietary or commercial disclosure may be found after the references.

To evaluate the longitudinal changes of retinal neurodegeneration and choroidal thickness in diabetic patients with and without diabetic retinopathy (DR).Prospective observational cohort study.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.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.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.

To investigate longitudinal changes in peripapillary choroidal thickness (pCT) and retinal nerve fiber thickness (pRNFLT) in patients with Type 2 diabetes mellitus.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.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, P0.05) 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.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.

Purpose Due to pubertal development and crystalline lens compensation, axial length (AL) continues to increase among non-progressive myopic children (absolute annual spherical equivalent (SE) progression less than 0.25 diopter), but the amount is unknown. This study was to investigate the cutoff of AL change to accurately differentiate between progressive and non-progressive myopes. Methods A total of 8,546 myopic and treatment-naive children aged 6–10 years were enrolled from two cohort studies. AL with optical biometer and cycloplegic SE with auto refraction were evaluated at baseline and annually. Annual AL change was calculated, and the percentiles of annual axial elongation among progressive and non-progressive myopes were estimated by quantile regression with restricted cubic spline. Area under receiver-operating characteristic (ROC) curve (AUROC), positive predictive value (PPV), and negative predictive value (NPV) were applied to evaluate the accuracy of predicting progressive and non-progressive myopes. Results Among 8,546 myopic children, 603 (7.06%) were non-progressive myopes. Annual AL changes among non-progressive myopes remained stable with the median annual change being 0.25 mm, while the median for progressive myopes decreased with age from 0.58 to 0.42 mm. AUROC for distinguishing between non-progressive and progressive myopes was 0.88 and was > 0.85 for each age group. Annual AL change, the cutoff of 0.20 mm/year, had significantly high PPV and NPV in predicting progressive myopes with high proportion of progressive myopes and non-progressive myopes with low proportions of progressive myopes. Conclusion Myopic children with non-progressive status had markedly less axial elongation than progressive ones. AL changes with cutoff of 0.20 mm/year could differentiate between non-progressive and progressive status and may be an alternative for evaluating progressive status.

Background The association of obstructive sleep apnea (OSA) with development of eye diseases is unclear. This current systematic review and meta-analysis attempts to summarize and analyze associations between OSA and ocular disorders in the literature. Methods PubMed, EMBASE, Google Scholar, Web Of Science, and Scopus databases were searched from 1901 to July 2022 in accordance with the Preferred Reporting in Systematic Review & Meta-Analysis (PRISMA). Our primary outcome assessed the association between OSA and the odds of developing floppy eyelid syndrome (FES), glaucoma, non-arteritic anterior ischemic optic neuropathy (NAION), retinal vein occlusion (RVO), keratoconus (KC), idiopathic intracranial hypertension (IIH), age-related macular degeneration (AMD), and central serous chorioretinopathy (CSR) through odds ratio calculated at the 95% confidence interval. Results Forty-nine studies were included for systematic review and meta-analysis. The pooled OR estimate was highest for NAION [3.98 (95% CI 2.38, 6.66)], followed by FES [3.68 (95% CI 2.18, 6.20)], RVO [2.71(95% CI 1.83, 4.00)], CSR [2.28 (95% CI 0.65, 7.97)], KC [1.87 (95% CI 1.16, 2.99)], glaucoma [1.49 (95% CI 1.16, 1.91)], IIH [1.29 (95% CI 0.33, 5.01)], and AMD [0.92 [95% CI 0.24, 3.58] All observed associations were significant (p Conclusion OSA is significantly associated with NAION, FES, RVO, CSR, KC, and glaucoma. Clinicians should be informed of these associations so early recognition, diagnosis, and treatment of eye disorders can be addressed in at-risk groups, and early referral to ophthalmic services is made to prevent vision disturbances. Similarly, ophthalmologists seeing patients with any of these conditions should consider screening and referring patients for assessment of possible OSA.

BACKGROUND Little is known about the prospective relationship between visual acuity (VA) and atherosclerotic cardiovascular disease (ASCVD) events, and the extent to which this association is mediated via potential mediators. OBJECTIVE To investigate the relationship between VA and ASCVD events, and to investigate the extent to which this association is mediated via potential mediators. METHODS A prospective population-based study analyzed data of participants aged 38-73 years from the UK Biobank cohort with baseline VA were included between 2006 and 2010. Habitual distance VA in the better-seeing eye was used for analysis. Data on ASCVD incidents was ascertained using hospital inpatient and death records until April 2021. Potential mediators used in the mediation analysis included hypertension, diabetes, depression and socioeconomic status. RESULTS Of 110,554 participants with available VA assessments and without ASCVD history at baseline, 61,518 (55.64%) were women and mean (SD) age was 56.43 (8.02) years. Over a median follow-up of 11.13 years, 5,496 cases of incident ASCVD were documented. After adjusting for all confounders, a one-line worse VA (0.1 LogMAR increase) was associated with an increased risk of incident ASCVD (HR= 1.62; 95%CI: 1.34-1.96, P < 0.001). In the mediation analysis, hypertension, diabetes, depression, and Townsend deprivation index attributed 3.8%, 3.3%, 5.7% and 5.9% to this association, respectively (all p-value for indirect effect < 0.05). Notably, the strongest indirect association was with depression and accounted for 10.0% (P for indirect effect < 0.05) of the association to ASVCD among women. CONCLUSIONS Our study demonstrates that visual decline is associated with an increased risk of ASCVD. We should intervene mediation factors in the early stage of vision decline through regular ophthalmic examination to reduce the ASCVD burden of the elderly, and attention should be paid to the impact of mental health on ASCVD, especially in older women. CLINICALTRIAL N/A

Background The integration of artificial intelligence (AI) and machine learning (ML) technologies into healthcare is transforming patient-practitioner interaction and could offer an additional platform for patient education and support. Objectives This study investigates whether ChatGPT-4 could provide safe and up-to date medical information about breast augmentation which is comparable to other patient information sources. Methods ChatGPT-4 was asked to generate 6 commonly asked questions regarding breast augmentation and respond to them. Its responses were qualitatively evaluated by a panel of specialist plastic and reconstructive surgeons and reconciled with a literature search of two large medical databases for accuracy, informativeness and accessibility. Results ChatGPT-4 provided well-structured, grammatically accurate, and comprehensive responses to the questions posed however it was limited in providing personalised advice and sometimes generated inappropriate or outdated references. ChatGPT consistently encouraged engagement with a specialist for specific information. Conclusions Although ChatGPT-4 showed promise as an adjunct tool in patient education regarding breast augmentation, there are areas requiring improvement. Additional advancements and software engineering are needed to enhance the reliability and applicability of AI-driven chatbots in patient education and support systems.

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.

Purpose The aim of this systematic review is to update and synthesize new evidence on BREAST-Q questionnaire’s ability to reflect patient-reported outcomes in women who have undergone breast reconstruction surgery (BRS) following mastectomy. Methods PubMed, Science Direct, Google Scholar, Cochrane CENTRAL, and Clincaltrial.gov were searched for relevant studies from January 2009 to September 2021. Any interventional or observational studies that used BREAST-Q to assess patient-reported outcomes in the assessment of BRS following mastectomy were included. Results A total of 42 studies were eligible for inclusion in the review. Three were randomized controlled trials and 39 were observational studies. Compared with pre-operative scores, there was an improvement in all BREAST-Q outcome domains following BRS including ‘satisfaction with breasts’, “satisfaction with outcome” “psychosocial”, “physical”, and “sexual wellbeing”. Sexual well-being had the lowest BREAST-Q score both pre-and post-operatively (37.8–80.0 and 39.0–78.0, respectively). Autologous BRS reports higher satisfaction and overall wellbeing compared to implant-based BRS. BREAST-Q has a higher and narrow internal consistency of 0.81 to 0.96 compared with other patient-reported outcome measures (PROMs; EORTC-QLQ, FACT-B, BR-23, BCTOS). The BREAST-Q questionnaire is the only PROM which allows patients to reflect on their care, surgical outcomes, and satisfaction collectively. Conclusion This review highlights the fact that BREAST-Q can effectively and reliably measure satisfaction and wellbeing of breast cancer patients after BRS. Comparatively, sexual wellbeing shows poorer outcomes following BRS and more longitudinal studies are necessary to understand the basis for these findings. Compared to other PROMs, BREAST-Q is reliable and specific to breast cancer surgery. Overall, BREAST-Q can help clinicians improve their quality of service, understand patient experiences, and may be used as an auditing tool for surgical outcomes.

The incidence of head and neck cutaneous squamous cell carcinoma (HNcSCC) is unevenly distributed between men and women. At present, the mechanism behind this disparity remains elusive. This study conducted a systematic review and meta-analysis of proportions to investigate the disparity between sexes for patients with HNcSCC. PubMed, Scopus, EMBASE, MEDLINE, Emcare and CINAHL were searched in November 2021 and June 2022 (N > 50, English, human), and studies which examined the association between sex and HNcSCC were included. Analysis was conducted using RStudio with data and forest plots displaying males as a proportion of total patients with HNcSCC. Two independent researchers performed study selection, data extraction, data analysis and risk of bias. Eighty-two studies (1948 to 2018) comprising approximately 186,000 participants (67% male, 33% female) from 29 countries were included. Significantly more males had HNcSCC overall (71%; CI: 67–74). Males were also significantly more affected by cSCC of the ear (92%; CI: 89–94), lip (74%; CI: 66–81), and eyelid (56%; CI: 51–62). This study found HNcSCC disproportionately affected males overall and across all subtypes. Improving our understanding of sex-specific mechanisms in HNcSCC will better inform our preventive, therapeutic and prognostic practices.

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.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.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).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.

To compare the treatment efficacy between repeated low-level red light (RLRL) therapy and 0.01% atropine eye drops for myopia control.A single-masked, single-center, randomized controlled trial was conducted on children 7 to 15 years old with cycloplegic spherical equivalent refraction (SER) ≤ -1.00 diopter (D) and astigmatism ≤ 2.50 D. Participants were randomly assigned to the RLRL group or low-dose atropine (LDA, 0.01% atropine eye drops) group and were followed up at 1, 3, 6, and 12 months. RLRL treatment was provided by a desktop light therapy device that emits 650-nm red light. The primary outcome was the change in axial length (AL), and the secondary outcome was the change in SER.Among 62 eligible children equally randomized to each group (31 in the RLRL group, 31 in the LDA group), 60 children were qualified for analysis. The mean 1-year change in AL was 0.08 mm (95% confidence interval [CI], 0.03-0.14) in the RLRL group and 0.33 mm (95% CI, 0.27-0.38) in the LDA group, with a mean difference (MD) of -0.24 mm (95% CI, -0.32 to -0.17; P0.001). The 1-year change in SER was -0.03 D (95% CI, -0.01 to -0.08) in the RLRL group and -0.60 D (95% CI, -0.7 to -0.48) in the LDA group (MD = 0.57 D; 95% CI, 0.40-0.73; P0.001). The progression of AL0.1 mm was 53.2% and 9.7% (P0.001) in the RLRL and LDA groups, respectively. For AL ≥ 0.36 mm, progression was 9.7% and 50.0% (P0.001) in the RLRL and LDA groups, respectively.In this study, RLRL was more effective for controlling AL and myopia progression over 12 months of use compared with 0.01% atropine eye drops.RLRL therapy significantly slows axial elongation and myopia progression compared with 0.01% atropine; thus, it is an effective alternative treatment for myopia control in children.

SummaryBackgroundThe retina is considered a unique window to systemic health, but their biological link remains unknown.MethodsA total of 93,838 UK Biobank participants with metabolomics data were included in the study. Plasma metabolites associated with GCIPLT were identified in 7,824 participants who also underwent retinal optical coherence tomography; prospective associations of GCIPLT-associated metabolites with 12-year risk of mortality and major age-related diseases were assessed in 86,014 participants. The primary outcomes included all- and specific-cause mortality. The secondary outcomes included incident type 2 diabetes mellitus (T2DM), obstructive sleep apnea/hypopnea syndrome (OSAHS), myocardial infarction (MI), heart failure, ischemic stroke, and dementia. C-statistics and net reclassification indexes (NRIs) were calculated to evaluate the added predictive value of GCIPLT metabolites. Calibration was assessed using calibration plots.FindingsSixteen metabolomic signatures were associated with GCIPLT (P< 0.009 [Bonferroni-corrected threshold]), and most were associated with the future risk of mortality and age-related diseases. The constructed meta-GCIPLT scores distinguished well between patients with high and low risks of mortality and morbidity, showing predictive values higher than or comparable to those of traditional risk factors (C-statistics: 0.780[0.771-0.788], T2DM; 0.725[0.707-0.743], OSAHS; 0.711[0.695-0.726], MI; 0.685[0.662-0.707], cardiovascular mortality; 0.657[0.640-0.674], heart failure; 0.638[0.636-0.660], other mortality; 0.630[0.618-0.642], all-cause mortality; 0.620[0.598-0.643], dementia; 0.614[0.593-0.634], stroke; and 0.601[0.585-0.617], cancer mortality). The NRIs confirmed the inclusion of GCIPLT metabolomic signatures to the models based on traditional risk factors resulted in significant improvements in model performance (5.18%, T2DM [P=3.86E-11]; 4.43%, dementia [P=0.003]; 4.20%, cardiovascular mortality [P=6.04E-04]; 3.73%, MI [P=1.72E-07]; 2.93%, OSAHS [P=3.13E-05]; 2.39%, all-cause mortality [P=3.89E-05]; 2.33%, stroke [P=0.049]; 2.09%, cancer mortality [P=0.039]; and 1.59%, heart failure [P=2.72E-083.07E-04]). Calibration plots showed excellent calibration between predicted risk and actual incidence in the new models.InterpretationGCIPLT-associated plasma metabolites captured the residual risk for mortality and major systemic diseases not quantified by traditional risk factors in the general population. Incorporating GCIPLT metabolomic signatures into prediction models may assist in screening for future risks of these health outcomes.FundingNational Natural Science Foundation (China).Research in contextEvidence before this studyRecent studies have recognized that retinal measurements can indicate an accelerated risk of aging and multiple systemic diseases preceding clinical symptoms and signs. Despite these insights, it remains unknown how retinal alterations are biologically linked to systemic health.Added value of this studyUsing the UK Biobank, we identified ganglion cell–inner plexiform layer thickness (GCIPLT) metabolomic signatures, and revealed their association with the risk of all- and specific-cause mortality and six age related diseases: type 2 diabetes, dementia, stroke, myocardial infarction, heart failure, and obstructive sleep apnea/hypopnea syndrome. The meta-GCIPLT score significantly improved the discriminative power of the predictive models for theses health outcomes based on conventional risk factors.Implications of all the available evidenceGCIPLT-associated plasma metabolites have the potential to capture the residual risk of systemic diseases and mortality not quantified by traditional risk factors. Incorporating GCIPLT metabolomic signatures into prediction models may assist in screening for future risks of these health outcomes. Since metabolism is a modifiable risk factor that can be treated medically, the future holds promise for the development of new strategies that reverse or interrupt the onset of these diseases by modifying metabolic factors.

Background Aberrant epigenetic modifications such as DNA methylation may contribute to the pathogenesis of DR. We aimed at elucidating the role of novel DNA methylation modifications in diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) using an extreme phenotypic design. Methods/results Two consecutive studies were conducted. A cross-sectional study using an extreme phenotypic design was conducted to identify rare methylation modifications that might contribute to DR pathogenesis. A 2-year longitudinal nested case–control study was conducted to validate the results and assess whether these novel methylation modifications could be used as biomarkers for predicting DR onset. A large number of differentially methylated CpG sites were identified in the cross-sectional study, and two (cg12869254 and cg04026387) corresponding to known genes were replicated in the longitudinal study. Higher methylation of cg12869254 significantly correlated with macular RNFL thinning in the superior and nasal subregions, and that of cg04026387 correlated with reduced deep capillary plexus VD in the superior and inferior subregions after adjusting for covariates. Conclusions Cg12869254 and cg04026387 hypermethylation may complement the known risk factors that contribute to the pathogenesis of DR and as novel biomarkers for disease prediction.

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.Prospective, observational cohort study.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 mmOver 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, P0.001) 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, P0.001) and DME occurrence (0.743 to 0.773, P=0.044). The estimated NRIs and IDIs (all0) indicated that the addition of CC FD% led to a significant improvement in the discriminative performance for endpoints.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.

ImportanceThe neural retina is considered a unique window to systemic health, but its biological link with systemic health remains unknown.ObjectiveTo 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 ParticipantsThis 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 MeasuresSystematic 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.ResultsAmong 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 P P P P P Conclusions and RelevanceIn 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.