Effect of intraocular pressure reduction on progressive high myopia (PHM study): study protocol of a randomised controlled trial.

BACKGROUND: In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation. OBJECTIVE: This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM). TRIAL DESIGN: Single-centre, open-label, prospective RCT. METHODS: This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests. ETHICS AND DISSEMINATION: Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05850936.

The landscape of angiogenesis and inflammatory factors in eyes with myopic choroidal neovascularization before and after anti-VEGF injection.

INTRODUCTION: To investigate the levels of angiogenesis and inflammatory cytokines in individuals with myopic choroidal neovascularization (mCNV) and the changes in these factors following intravitreal anti-VEGF injection. METHODS: Aqueous humor samples were gathered from eyes with mCNV, those with single macular bleeding (SMB) without mCNV in highly myopic eyes, and those with age-related cataracts. Using a multiplex bead immunoassay, we analyzed 28 angiogenesis and inflammatory factors in the aqueous humor. Furthermore, clinical data were documented for correlation analysis. RESULTS: In this study, the levels of vascular endothelial growth factor A (VEGF-A), interleukin 8 (IL-8), and fibroblast growth factors 1 (FGF-1) were significantly elevated in mCNV compared to SMB eyes (p < 0.05). Their odds ratios for mCNV occurrence were 1.05, 3.45, and 2.64, respectively. Hepatocyte growth factor (HGF) and VEGF-C were notably higher in mCNV than in cataract patients (p < 0.05), and VEGF-C correlated to the degree of myopic atrophic maculopathy (p = 0.024). Axial length exhibited a negative correlation with VEGF-A and positive correlations with VEGF-C, HGF, and MCP-1 (p < 0.01). Following anti-VEGF treatment, a reduction in VEGF-A, endothelin-1, and FGF-2 was noted in mCNV patients (p < 0.05), but MCP-1 levels increased. CONCLUSION: Our findings highlight the predominant role of angiogenesis and inflammation factors in mCNV pathogenesis. VEGF-C's correlation with axial length and atrophy suggests its involvement in the process of myopic atrophic maculopathy.

Risk factors and patterns for progression of fellow-eye myopic traction maculopathy: a 3-year retrospective cohort study.

AIMS: To investigate the effect of preretinal tractional structures (PTS) and posterior scleral structures (PSS) on myopic traction maculopathy (MTM) progression. METHODS: This retrospective cohort study included 185 fellow highly myopic eyes of 185 participants who underwent surgery for MTM. PTS included epiretinal membrane, incomplete posterior vitreous detachment and their combination. PSS included posterior staphyloma and dome-shaped macula (DSM). The MTM stage was graded according to the Myopic Traction Maculopathy Staging System. Optical coherence tomography was used to identify MTM progression, defined as an upgrade of MTM. The Kaplan-Meier method with log-rank test was used to assess MTM progression over the 3-year follow-up period. Risk factors for progression were identified using Cox regression analysis. RESULTS: MTM progression was observed in 48 (25.9%) eyes. Three-year progression-free survival (PFS) rates for eyes with PTS, staphyloma and DSM were 53.7%, 58.2% and 90.7%, respectively. Eyes with PTS and staphyloma exhibited lower 3-year PFS rates than those without PTS or staphyloma (P log-rank test =0.002 and <0.001), while eyes with DSM had a higher 3-year PFS rate than eyes without DSM (P log-rank test=0.01). Multivariate Cox regression analysis showed that PTS (HR, 3.23; p<0.001) and staphyloma (HR, 7.91; p<0.001) were associated with MTM progression, whereas DSM (HR, 0.23; p=0.046) was a protective factor. CONCLUSION: Both PTS and PSS play a critical role in the progression of MTM. Addressing these factors can aid in the management of MTM.

METAVISION: a novel system for quantifying metamorphopsia in patients with myopic traction maculopathy.

PURPOSE: To develop a novel system for quantifying metamorphopsia in patients with myopic traction maculopathy (MTM) and to explore the metamorphopsia pattern of MTM. DESIGN: Observational, cross-sectional study. METHODS: We designed a new system. RESULTS: Of the 445 eyes tested, 188 (42.25%) were deemed by patients to have metamorphopsia impacting their daily lives while 257 (57.75%) were considered to have no metamorphopsia symptoms. The Amsler grid, M-CHARTS and METAVISION tests displayed sensitivities for metamorphopsia of 95.74%, 89.89% and 100%, respectively. The specificities of the Amsler grid, M-CHARTS and METAVISION tests are 100%. The metamorphopsia questionnaire and METAVISION scores were highly consistent (average intraclass correlation coefficient=0.951, p<0.001) and strongly correlated (R=0.879, p<0.001). The METAVISION score was highly correlated with the stages of MTM (R=0.837, p<0.001), whereas there was a moderate correlation between the M-CHARTS M-score and the stages of MTM (R=0.679, p<0.001). CONCLUSIONS: Quantification of metamorphopsia is important and useful for MTM management. The METAVISION is a clinically applicable and comprehensive approach for quantifying metamorphopsia, which can be used in clinical settings.

Optic neuropathy in high myopia: Glaucoma or high myopia or both?

Due to the increasing prevalence of high myopia around the world, structural and functional damages to the optic nerve in high myopia has recently attracted much attention. Evidence has shown that high myopia is related to the development of glaucomatous or glaucoma-like optic neuropathy, and that both have many common features. These similarities often pose a diagnostic challenge that will affect the future management of glaucoma suspects in high myopia. In this review, we summarize similarities and differences in optic neuropathy arising from non-pathologic high myopia and glaucoma by considering their respective structural and functional characteristics on fundus photography, optical coherence tomography scanning, and visual field tests. These features may also help to distinguish the underlying mechanisms of the optic neuropathies and to determine management strategies for patients with high myopia and glaucoma.

DIFFERENCES IN THE PROGRESSION BETWEEN MYOPIC MACULOSCHISIS EYES WITH AND WITHOUT MACULAR DETACHMENT IN THE NATURAL COURSE OF THE DISEASE: A Retrospective Longitudinal Study Based on the New Myopic Traction Maculopathy Staging System.

PURPOSE: To investigate the pace of visual acuity loss in myopic maculoschisis eyes with or without macular detachment and identify associated risk factors. METHODS: One thousand three hundred and thirty-four eyes of 991 patients with high myopia were reviewed. A new myopic traction maculopathy staging system classified four retinal stages and three foveal stages. To the myopic traction maculopathy eyes with normal fovea, maculoschisis with and without macular detachment was defined as Stage 3a and Stages 1a, 2a respectively. RESULTS: One hundred and ten (8.25%) eyes with maculoschisis were included, with a follow-up of 24.00 ± 17.47 months. Of them, 84 (76.36%) were Stages 1a, 2a, and 26 (23.64%) were Stage 3a. The visual acuity loss per year during the follow-up period was similar between eyes with Stages 1a, 2a and Stage 3a (3.13 ± 12.21 vs. 3.41 ± 18.42 letters, P = 0.930). Multivariate analyses revealed that vitreomacular interface factors were significantly associated with visual acuity loss during the follow-up, no matter in Stages 1a, 2a or Stage 3a ( P = 0.039 and P = 0.038, respectively). In the Stages 1a, 2a group, the percentage of eyes that lost at least 10 letters at the final visit compared with the baseline visual acuity was higher in eyes with vitreomacular interface factors than in those without vitreomacular interface factors (13 eyes, 50.00% vs. 14 eyes, 24.14%, P = 0.019). CONCLUSION: No differences were found in visual acuity loss pace between Stages 1a, 2a and Stage 3a. Surgical intervention or at least more intensive follow-up should be considered for Stages 1a, 2a eyes with vitreomacular interface factors, to promote a more favorable visual outcome.

Evaluation of a self-imaging OCT for remote diagnosis and monitoring of retinal diseases.

OBJECTIVES: To evaluate the feasibility and accuracy of a portable, self-imaging optical coherence tomography (OCT) for measuring central subfield thickness (CST) and achieving diagnostic concordance for retinal lesions compared with clinic-based spectral-domain OCT (SD-OCT). METHODS: This comparative, cross-sectional study was conducted between August 2020 and February 2021. Two groups of adult participants were recruited: (1) a selected cohort of 160 participants with confirmed diagnosis and (2) a consecutive cohort of 315 participants recruited randomly. All participants underwent self-imaging OCT examination, as well as standard OCT examination. CST was automatically calculated for comparisons between the two OCT devices. Diagnostic concordance for retinal lesions and the success rate of self-imaging were assessed within the consecutive cohort. RESULTS: In the selected cohort, self-imaging OCT images yielded consistent CST with SD-OCT, with a mean difference of 0.1±7.7 µm for normal eyes, 4.9±10.6 µm for macular oedema, -1.3±9.5 µm for choroidal neovascularisation, 5.0±7.8 µm for epiretinal membrane. The self-imaging OCT also demonstrated good repeatability, with a mean test-retest difference in CST of 0.7±3.9 µm and limits of agreement ranging from -6.9 to 8.3 µm. Additionally, within the consecutive cohort, interdevice κ values ranged for detecting various retinal lesions ranged from 0.8 to 1.0, except in the cases of retinal detachment (κ=0.5). All eyes (100%) in the selected cohort and 242 eyes (76.8%) in the consecutive cohort successfully completed self-imaging. Participants spent less time on self-imaging compared with SD-OCT operated by a technician (66.7±20.1 vs 73.3±32.5, p<0.01). A majority of participants (90%) found the self-imaging process 'easy' and 'comfortable'. CONCLUSIONS AND RELEVANCE: This study demonstrates that our self-imaging OCT and clinical-used SD-OCT are highly consistent not only in measuring the CST but also in identifying most retinal lesions.

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.

Optic Nerve Head Abnormalities in Nonpathologic High Myopia and the Relationship With Visual Field.

PURPOSE: To describe the optic nerve head (ONH) abnormalities in nonpathologic highly myopic eyes based on swept-source optical coherence tomography (OCT) and the relationship with visual field (VF). DESIGN: Secondary analysis from a longitudinal cohort study. METHODS: Highly myopic patients without myopic maculopathy of category 2 or higher were enrolled. All participants underwent a swept-source OCT examination focused on ONH. We differentiated between 3 major types (optic disc morphologic abnormality, papillary/peripapillary tissue defect, and papillary/peripapillary schisis) and 12 subtypes of ONH abnormalities. The prevalence and characteristics of ONH abnormalities and the relationship with VF were analyzed. RESULTS: A total of 857 participants (1389 eyes) were included. Among the 1389 eyes, 91.86%, 68.61%, and 34.92% of them had at least 1, 2, or 3 ONH abnormalities, respectively, which corresponded to 29.55%, 31.79%, and 35.67% of VF defects, respectively. Among the 12 subtypes of the 3 major types, peripapillary hyperreflective ovoid mass-like structure, visible retrobulbar subarachnoid space, and prelaminar schisis were the most common, respectively. Perimetric defects corresponding to OCT abnormalities were more commonly found in eyes with peripapillary retinal detachment, peripapillary retinoschisis, and peripapillary hyperreflective ovoid mass-like structure. Glaucoma-like VF defects were more common in eyes with deep optic cups (28.17%) and with optic disc pit/pit-like change (18.92%). CONCLUSIONS: We observed and clarified the ONH structural abnormalities in eyes with nonpathologic high myopia. These descriptions may be helpful to differentiate changes in pathologic high myopia or glaucoma.

Integrated Transcriptome Analysis of Long Noncoding RNA and mRNA in Developing and Aging Mouse Retina.

Mice have emerged as a widely employed model for investigating various retinal diseases. However, the availability of comprehensive datasets capturing the entire developmental and aging stages of the mouse retina, particularly during the elderly period, encompassing integrated lncRNA and mRNA expression profiles, is limited. In this study, we assembled a total of 18 retina samples from mice across 6 distinct stages of development and aging (5 days, 3 weeks, 6 weeks, 10 weeks, 6 months, and 15 months) to conduct integrated lncRNA and mRNA sequencing analysis. This invaluable dataset offers a comprehensive transcriptomic resource of mRNA and lncRNA expression profiles during the natural progression of retinal development and aging. The discoveries stemming from this investigation will significantly contribute to the elucidation of the underlying molecular mechanisms associated with various retinal diseases, such as congenital retinal dysplasia and retinal degenerative diseases.

Effect of Extracurricular After-School Physical Activities on Academic Performance of Schoolchildren: A Cluster Randomized Clinical Trial.

Importance: The beneficial effects of increasing outdoor physical activity time on children's myopia onset and physical well-being are widely acknowledged. However, in countries with competitive educational systems, such as China, parents and school administrators may be relatively reluctant to increase the extracurricular physical activity time for children due to concerns that this action will compromise children's academic performance. Objective: To investigate whether additional extracurricular physical activity time after school compromises the academic performance of schoolchildren. Design, Setting, and Participants: This cluster randomized clinical trial was conducted from October 2020 to June 2021 in Yudu, Jiangxi, China. Eligible children in grades 3 and 4 from 24 elementary schools were randomized to the intervention or control group. Primary analysis was conducted in the full sample using the intention-to-treat principle. Interventions: The intervention group received 2 hours of after-school physical activity time outdoors on school days. The control group was free to arrange their after-school activity. Main Outcomes and Measures: The primary outcome was the between-group mean difference in mathematics test scores at the end of 1 academic year, with a noninferiority margin of -3.3 points. Standardized mathematics tests, physical fitness assessments (in reference to the 2018 National Physical Fitness Survey Monitoring Programme in China), and cycloplegic autorefraction were performed at baseline and the end of 1 academic year. Myopia was defined as a cycloplegic spherical equivalent refraction of -0.5 diopters or less in either eye. Results: A total of 2032 children (mean [SD] age, 9.22 [0.62] years; 1040 girls [51.2%]) from 24 schools were randomized to the intervention group (12 schools; 1012 children) or control group (12 schools; 1020 children). The mean (SD) mathematics score at the end of 1 academic year was 78.01 (17.56) points in the intervention group and 77.70 (17.29) points in the control group. The adjusted between-group mean difference was 0.65 points (95% CI, -2.85 to 4.15). The adjusted between-group mean difference in physical fitness score was 4.95 points (95% CI, 3.56-6.34; P < .001) and -1.90% (95% CI, -18.72% to 14.91%; P > .99) in myopia incidence. Conclusions and Relevance: Results of this trial indicate that, compared with the control practice of free play after school, adding 2 hours of extracurricular physical activity outdoors after school was noninferior in academic performance and had superior efficacy in improving physical fitness. Trial Registration: ClinicalTrials.gov Identifier: NCT04587765.

Assessment of Ocular Deformation in Pathologic Myopia Using 3-Dimensional Magnetic Resonance Imaging.

IMPORTANCE: Ocular deformation in pathologic myopia can affect the entire globe. However, few studies have investigated the equatorial pattern of ocular shape. In addition, the correlation between equatorial and posterior morphology needs to be further explored. OBJECTIVE: To assess global ocular deformation in pathologic myopia. DESIGN, SETTING, AND PARTICIPANTS: This hospital-based, cross-sectional study included 180 pathologic myopic eyes with atrophic maculopathy grading C2 (diffuse chorioretinal atrophy) or more from 180 participants who underwent comprehensive ophthalmic examination, including high-resolution 3-dimensional magnetic resonance imaging. In addition, 10 nonpathologic myopic eyes of 10 participants were set as the control group. Main Outcomes and Measures: According to the cross-sectional view of equator, equatorial shape was classified as round, rectangular, pyriform (noncircular and more protruded in 1 direction), vertical-elliptical, or horizontal-elliptical; according to the nasal and inferior views, the posterior shape was categorized as spheroidal, conical, bulb-shaped, ellipsoidal, multidistorted, and barrel-shaped. Equatorial circularity and ocular sphericity were used to quantitatively assess the morphological variability of the equatorial and posterior regions, respectively. The association between ocular morphology and ocular parameters and myopic maculopathy was also investigated. Results: The mean (SD) age of 180 participants with pathologic myopia was 55.14 (10.74) years, 127 were female (70.6%), and the mean (SD) axial length of studied eyes was 30.22 (2.25) mm. The predominant equatorial shape was pyriform (66 eyes [36.7%]), followed by round (45 eyes [25.0%]). The predominant posterior shape was bulb-shaped (97 eyes [52.2%]), followed by multidistorted (46 eyes [24.7%]). Equatorial circularity and equatorial shapes were correlated (r = -0.469; 95% CI, -0.584 to -0.346; P < .001) and ocular sphericity was correlated with posterior shapes (r = -0.533; 95% CI, -0.627 to -0.427; P < .001). In eyes with a vertical-elliptical equator, equatorial circularity and ocular sphericity were positively linearly correlated (R2 = 0.246; 95% CI, 0.050-0.496; P = .002) and the prevalence of inferior staphyloma was higher (27.8%; P = .04). Eyes with a horizontal-elliptical equator have the most horizontally oriented axis of corneal flat keratometry (median, 43.55 [interquartile range, 43.84] degrees; P = .01) and tended to present with multidistorted posterior shape (21.7%; P = .04). Conclusions and Relevance: These findings suggest ocular deformation is common in pathologic myopia and can affect the entire eye, including the equatorial and posterior regions. The morphological classification may enhance the understanding of the diverse patterns of ocular shape in pathologic myopia.

High Myopia Normative Database of Peripapillary Retinal Nerve Fiber Layer Thickness to Detect Myopic Glaucoma in a Chinese Population.

PURPOSE: To develop and validate the performance of a high myopia (HM)-specific normative database of peripapillary retinal nerve fiber layer (pRNFL) thickness in differentiating HM from highly myopic glaucoma (HMG). DESIGN: Cross-sectional multicenter study. PARTICIPANTS: A total of 1367 Chinese participants (2325 eyes) with nonpathologic HM or HMG were included from 4 centers. After quality control, 1108 eyes from 694 participants with HM were included in the normative database; 459 eyes from 408 participants (323 eyes with HM and 136 eyes with HMG) and 322 eyes from 197 participants (131 eyes with HM and 191 eyes with HMG) were included in the internal and external validation sets, respectively. Only HMG eyes with an intraocular pressure > 21 mmHg were included. METHODS: The pRNFL thickness was measured with swept-source (SS) OCT. Four strategies of pRNFL-specified values were examined, including global and quadrantic pRNFL thickness below the lowest fifth or the lowest first percentile of the normative database. MAIN OUTCOMES MEASURES: The accuracy, sensitivity, and specificity of the HM-specific normative database for detecting HMG. RESULTS: Setting the fifth percentile of the global pRNFL thickness as the threshold, using the HM-specific normative database, we achieved an accuracy of 0.93 (95% confidence interval [CI], 0.90-0.95) and 0.85 (95% CI, 0.81-0.89), and, using the first percentile as the threshold, we acheived an accuracy of 0.85 (95% CI, 0.81-0.88) and 0.70 (95% CI, 0.65-0.75) in detecting HMG in the internal and external validation sets, respectively. The fifth percentile of the global pRNFL thickness achieved high sensitivities of 0.75 (95% CI, 0.67-0.82) and 0.75 (95% CI, 0.68-0.81) and specificities of 1.00 (95% CI, 0.99-1.00) and 1.00 (95% CI, 0.97-1.00) in the internal and external validation datasets, respectively. Compared with the built-in database of the OCT device, the HM-specific normative database showed a higher sensitivity and specificity than the corresponding pRNFL thickness below the fifth or first percentile (P < 0.001 for all). CONCLUSIONS: The HM-specific normative database is more capable of detecting HMG eyes than the SS OCT built-in database, which may be an effective tool for differential diagnosis between HMG and HM. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Brain and Cognition Signature Fingerprinting Vascular Health in Diabetic Individuals: An International Multi-Cohort Study.

OBJECTIVE: To evaluate the correlation between cognitive signatures and the risk of diabetic vascular complications and mortality, based on a multicountry prospective study. METHODS: The participants comprised 27,773 diabetics from the UK Biobank (UKB) and 1307 diabetics from the Guangzhou Diabetic Eye Study (GDES) cohort. The exposures were brain volume and cognitive screening tests for UKB participants, whilst the global cognitive score (GCS) measuring orientation to time and attention, episodic memory, and visuospatial abilities were determined for GDES participants. The outcomes for the UKB group were mortality, as well as macrovascular (myocardial infarction [MI] and stroke), microvascular (end-stage renal disease [ESRD], and diabetic retinopathy [DR]) events. The outcomes for the GDES group were retinal and renal microvascular damage. RESULTS: In the UKB group, a 1-SD reduction in brain gray matter volume was associated with 34%-77% higher risks of incident MI, ESRD, and DR. The presence of impaired memory was associated with 18%-73% higher risk of mortality and ESRD; impaired reaction was associated with 1.2-1.7-fold higher risks of mortality, stroke, ESRD, and DR. In the GDES group, the lowest GCS tertile exhibited 1.4-2.2-fold higher risk of developing referable DR and a twofold faster decline in renal function and retinal capillary density compared with the highest tertile. Restricting data analysis to individuals aged less than 65 years produced consistent results. CONCLUSION: Cognitive decline significantly elevates the risk of diabetic vascular complications and is correlated with retinal and renal microcirculation damage. Cognitive screening tests are strongly recommended as routine tools for management of diabetes.

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.

PSMD3 gene mutations cause pathological myopia.

PURPOSE: Genetic factors play a prominent role in the pathogenesis of pathological myopia (PM). However, the exact genetic mechanism of PM remains unclear. This study aimed to determine the candidate mutation of PM in a Chinese family and explore the potential mechanism. METHODS: We performed exome sequencing and Sanger sequencing in a Chinese family and 179 sporadic PM cases. The gene expression in human tissue was investigated by RT-quantitative real-time PCR (RT-qPCR) and immunofluorescence. Cell apoptotic rates were tested by annexin V-APC/7AAD and flow cytometry. Psmd3 knock-in mice with point mutation were generated for measuring myopia-related parameters. RESULTS: We screened a novel PSMD3 variant (c.689T>C; p.F230S) in a Chinese family with PM, and another rare mutation (c.1015C>A; p.L339M) was identified in 179 unrelated cases with PM. RT-qPCR and immunofluorescence confirmed the expression of PSMD3 in human eye tissue. Mutation of PSMD3 decreased the mRNA and protein expression, causing apoptosis of human retinal pigment epithelial cells. In in vivo experiments, the axial length (AL) of mutant mice increased significantly compared with that of wild-type mice (p<0.001). CONCLUSIONS: A new potential pathogenic gene, PSMD3, in a PM family was identified, and it may be involved in the elongation of AL and the development of PM.

Macular buckling alone versus combined inverted ILM flap on macular hole-associated macular detachment in patients with high myopia.

PURPOSE: To compare the efficacy of macular buckling (MB) alone against a combined internal limiting membrane (ILM) inversion flap for full-thickness macular hole (FTMH)-associated macular detachment (MD) in patients with high myopia. METHODS: This was a prospective interventional case series of patients with high myopia surgically treated with MB alone or combined with an inverted ILM flap for FTMH- associated MD. Best-corrected visual acuity (BCVA) at the 24-month postoperative follow-up, rate of initial retinal reattachment and macular hole closure were measured. RESULTS: A total of 62 eyes from 62 participants (33 in the MB group, 29 in the combination group) were studied. Postoperative BCVA improved significantly in both the combination group (P < 0.001) and the MB group (P = 0.027). The postoperative BCVA at 12 months (P = 0.021) and 24 months (P = 0.041) was significantly better in the combination group than in the MB group. The postoperative BCVA was not significantly different between the eyes with closed and unclosed MH at each follow-up time point (P > 0.05). In the combination group, we observed earlier retinal reattachment and closure of the MH as well as a higher rate of MH closure (82.8% vs. 66.7%) than in the MB group, although this difference was insignificant (P = 0.248). CONCLUSION: MB combined with the ILM flap inversion technique achieved better postoperative BCVA and a higher success rate of MH closure than MB alone. We believe that combination surgery should be preferentially recommended.

Longitudinal Changes in Lens Thickness and Lens Power Among Persistent Non-Myopic and Myopic Children.

Purpose: To assess the longitudinal changes in crystalline lens in persistent non-myopic and myopic children. Methods: Four cohorts of children were recruited from Guangzhou, China, from first year of kindergarten (G0, n = 1129), first year of primary school (G1, n = 1324), fourth year of primary school (G4, n = 1854), and first year of junior high school (G7, n = 867) in 2018 and followed up annually for 2 years. All children received cycloplegic autorefraction and ocular biometry measurement. Children were classified into categories of persistent non-myopia (PNM; spherical equivalent refraction [SER] ≥-0.5 diopter [D] at baseline and during follow-up), persistent myopia (PM; SER <-0.5 D at baseline and during follow-up), or newly developed myopia (NDM: SER ≥-0.5 D at baseline and <-0.5 D during follow-up). Results: The mean (SD) age was 3.69 (0.34) years for children in G0, 6.79 (0.35) years in G1, 9.52 (0.42) years in G4, and 12.56 (0.38) years in G7. A LOWESS plot showed a three-stage pattern of change in lens thickness (LT) in PNM children including a rapid decrease from 3 to 7 years of age and a slower decrease from 7 to 11 years, followed by an increase thereafter. Similar trends were observed in the PM and NDM groups, although there was less change in LT. In contrast, lens power (LP) decreased consistently in all cohorts during the follow-up. No significant changes in LT or LP were observed around myopia onset. Conclusions: The lens showed a three-stage pattern of change in LT, whereas there was continuous loss of LP in children ages 3 to 15 years.

Axial Growth Driven by Physical Development and Myopia among Children: A Two Year Cohort Study.

Background: The physical process of axial length growth among children and its role in the occurrence of myopia remain insufficiently explored. In this study, we investigate the patterns of ocular axial growth among persistent myopia (PM) and persistent non-myopia (PNM) children aged 3 to 15 years. Methods: A group of 6353 children aged 3 to 15 years, selected from rural schools in China, were followed up annually for 2 years. Biometric measurements including axial length (AL) and spherical equivalent refraction (SER) were obtained. Body height was recorded. Children were divided into two groups: PM group defined as SER of −0.50 D or less; PNM group defined as −0.50 D < SER < +3.0 D during follow-up. Results: Annual AL growth was fairly consistent for PNM eyes of children aged 3 to 11 years and then reduced significantly (independent t test, p < 0.001) for children aged 12 years and older. This pattern of AL changes was similar for PM children, although the AL growth was greater among them. Among children aged 6 and older, body height change was concomitant to AL growth (p < 0.01) and SER myopic shift (p < 0.001) until reaching 12 years old (p = 0.308 and p = 0.679, respectively). Conclusions: Stature growth and AL growth are both remarkable and consistent and concomitant but start to attenuate when the children reach 10 to 12 years old among emmetropic children. This observation suggests that AL growth is driven by physical development until 12 years old, whereas its excessive growth is dominated by myopia development.