Importance:The highly myopic eye remodels in 3 dimensions, but the longitudinal trajectories of globe shape and their associations with sight-threatening outcomes remain poorly defined. Objective:To characterize 15-year 3-dimensional (3D) remodeling trajectories of highly myopic globes and examine their associations with baseline features and ocular outcomes. Design, Setting, and Participants:This 15-year 3D magnetic resonance imaging (MRI) cohort substudy was nested within the Zhongshan High Myopia Cohort. Thirty participants (60 eyes) with bilateral high myopia (spherical equivalent refraction, -6.00 D or worse) randomly drawn from 95 participants imaged in September 2011 were rescanned in September 2025. Exposures:Orbital 3D MRI reconstructions were classified into 6 globe-shape categories. Paired classifications, global enlargement, and staphyloma status defined 5 remodeling patterns: quiescence, proportional expansion, focal emergence, focal progression, and shape transition. Main Outcomes and Measures:Distribution of remodeling patterns and their associations with myopic macular degeneration (MMD), myopic traction maculopathy (MTM), posterior staphyloma (PS), visual acuity, and visual field indices. Results:Among the 30 included participants, the mean (SD) age was 37.30 (15.89) years, and 16 (53.3%) participants were women. The 60 eyes were classified as quiescent (21 [35.0%]), proportional expansion (12 [20.0%]), focal emergence (14 [23.3%]), focal progression (6 [10.0%]), or shape transition (7 [11.7%]). No deformed eye reverted to spheroidal. Pattern distribution was associated with baseline age and contour: 10 of 12 eyes (83.3%) of individuals younger than 20 years underwent proportional expansion, whereas 13 of 24 eyes (54.2%) of individuals aged 40 years and older followed focal progression or shape transition. Eyes with focal emergence had the largest best-corrected visual acuity decline (0.26 logMAR) and mean deviation worsening (-3.50 dB), and eyes with shape transition had the largest pattern standard deviation increasing (1.95 dB). At similar axial elongation, eyes developing focal deformation had higher frequencies of MMD progression (91.7%; 95% CI, 74.2-97.7 vs 58.8%; 95% CI, 36.0-78.4; P = .02), incident or progressive PS (91.7%; 95% CI, 74.2-97.7 vs 17.6%; 95% CI, 6.2-41.0; P < .001), and MTM (58.3%; 95% CI, 38.8-75.5 vs 11.8%; 95% CI, 3.3-34.3; P = .003). Conclusions and Relevance:Highly myopic globes followed age- and geometry-associated trajectories linked to outcomes beyond axial elongation. These 2-time-point findings potentially support 3D shape analysis as a candidate framework for individualized surveillance, pending prospective validation.

PURPOSE:To investigate the origin, intraocular distribution, and metabolism of insulin in the eye and elucidate its relationship with high myopia. METHODS:Insulin localization in rat retinas was determined through immunofluorescence. Primary Müller cells from rat and human retinas were characterized to assess insulin expression. FITC-labeled insulin was administered via tail vein and intravitreal injections to evaluate transport dynamics. Vitreous samples from patients with varying macular pathologies were analyzed for insulin, C-peptide, and glucose levels, comparing high myopia patients with controls. Form-deprived guinea pigs underwent insulin and glucose quantification with insulin intervention experiments. RESULTS:In patients with macular hole, high myopia patients showed significantly higher vitreous insulin (1.5-fold, p < 0.01) and C-peptide (1.8-fold, p < 0.001), with lower glucose (19%, p < 0.01) versus controls. Human vitreous insulin also correlated positively with macular pathology severity (p < 0.001). Insulin expression colocalized with Müller cell markers; Ins1/Ins2 mRNA was upregulated by serum deprivation. FITC tracing in SD rat showed that systemic insulin failed to penetrate the blood-retinal barrier, while intravitreal insulin primarily accumulated at the inner limiting membrane. Form-deprived guinea pigs mirrored this metabolic signature (higher insulin, lower glucose). Critically, exogenous insulin administration did not affect myopia progression (p > 0.05). CONCLUSIONS:Müller cells produce insulin locally, creating a distinct intraocular environment. High myopia is associated with elevated insulin production with enhanced glucose utilization, but exogenous insulin did not significantly accelerate axial elongation, suggesting it is insufficient to further exacerbate myopia progression in this model.

Microglia are central regulators of retinal immune homeostasis, yet their pathogenic states in retinal degeneration remain less well understood. Here we identified a distinct subset of lipid-accumulated reactive microglia (aLARM), using scRNA sequencing and spatial transcriptomics in NaIO3-induced retinal degeneration mice, predominantly localized to the outer retina. aLARM were conserved across mouse models and patients and uniquely marked by high CD36 expression. Microglia-specific CD36 deletion abolished aLARM-mediated inflammation and degeneration, whereas subretinal transplantation of CD36+ aLARM exacerbated retinal structural destruction and functional impairment. Mechanistically, CD36+ aLARM activated NLRP3 inflammasome and produced IL-1β, engaging IL-1R1 on microglia/macrophages and pericytes/SMCs to amplify a feed-forward inflammatory circuit. Therapeutic CD36 blockade with the neutralizing antibody FA6-152 reduced aLARM formation and protected against neurodegeneration. Together, our findings highlight CD36+ aLARM as a targetable pathogenic microglial population linking neuroinflammation to retinal degeneration, providing a potential foundation for microglia-based precision therapies. Metabolic stress can reshape immune cells into drivers of tissue damage. This study identifies CD36-driven lipid accumulation in reactive microglia as a mechanism linking retinal inflammation to degeneration.

AIMS:To identify early oculomic biomarkers predictive of pathologic myopia (PM) in children with high myopia (HM) and to develop an artificial intelligence (AI)-based model for individualised risk stratification. METHODS:This prospective longitudinal study included 375 children with bilateral HM (spherical equivalent ≤ -6.00 dioptres (D)) from the Zhongshan High Myopia Cohort, followed for a median of 15.0 years (IQR, 14.9-15.4; range, 14.7-15.7). Deep learning-based automated retinal vascular phenotyping was applied to fundus photographs and integrated with longitudinal ocular biometry and swept-source optical coherence tomography metrics. Multivariable models identified independent predictors of PM onset and predictive performance was assessed using area under the receiver operating characteristic curve (AUROC). A web-based prediction tool was developed for clinical deployment. RESULTS:PM developed in 64 children (17.1%). Independent predictors included lower retinal vessel density (OR, 9.69; 95% CI 4.33 to 21.70), reduced fractal dimension (OR, 5.94; 95% CI 3.07 to 11.50), narrower arteriolar and venular calibres (central retinal arteriolar equivalent: OR, 3.44; 95% CI 1.86 to 6.34; central retinal venular equivalent: OR, 4.42; 95% CI 2.24 to 8.71), thinner subfoveal choroid (OR, 2.64; 95% CI 1.56 to 4.45), faster early axial elongation (OR, 1.72; 95% CI 1.17 to 2.50) and accelerated early choroidal thinning (OR, 2.33; 95% CI 1.41 to 3.84). The AI oculomic model achieved excellent discrimination (AUROC, 0.96; 95% CI 0.92 to 1.00), improving to 0.98 (95% CI 0.95 to 1.00) with biometric variables. These predictors were implemented in a publicly accessible risk prediction platform (System for Myopia AI-based Risk Tracking-PM). CONCLUSIONS:PM risk in paediatric HM is detectable early through retinal microvascular architecture and ocular growth dynamics. AI-enabled oculomic profiling offers a scalable approach to early risk stratification, supporting targeted surveillance and timely prevention of sight-threatening pathology.

BACKGROUND:Retinal neurodegeneration is an early and independent feature of diabetic retinal disease and has been proposed as a window into the systemic neural consequences of diabetes, yet accessible molecular biomarkers and individualized prediction tools remain scarce. We aimed to identify circulating plasma protein signatures of diabetic retinal neurodegeneration (DRN) and to translate them into a clinically usable risk prediction system. METHODS AND FINDINGS:In this multi-cohort prospective observational study, we integrated high-throughput plasma proteomics with longitudinal optical coherence tomography (OCT) in two independent populations. The discovery cohort comprised 1,492 participants had baseline plasma proteomics and OCT, and 1,218 were followed with repeated OCT over 6 years in Guangzhou Diabetic Eye Study (GDES). DRN was quantified by the annualized OCT-derived retinal nerve fiber layer thinning rate. In multivariable analyses adjusted for age, sex, smoking, systolic blood pressure, HbA1c, and diabetes duration, we identified 71 plasma proteins associated with development and progression of DRN. These proteins mapped onto pathways governing inflammatory immune recruitment, extracellular matrix remodeling, and microvascular homeostasis, providing a plausible biological basis for DRN. We developed a proteomics-based DRN model (Pro-DRN) using eight machine learning (ML) algorithms, including XGBoost and LightGBM. In the independent test set, Pro-DRN achieved a C-index of 0.860, rising to 0.908 when integrated with clinical variables. Compared with six conventional models, Pro-DRN improved discrimination (ΔC-index 0.137 to 0.159; all P < 0.001), reclassification (IDI 0.212 to 0.245; NRI 0.226 to 0.452; all P < 0.05). In the Hippisley model, the C-index increased from 0.739 (95% CI [0.670, 0.808]) to 0.898 (95% CI [0.858, 0.937]), with IDI 0.245 (95% CI [0.177, 0.318]), NRI 0.452 (95% CI [0.222, 0.673]) (both P < 0.001), and higher net benefit. The proteins most consistently driving model performance included ACTA2, COL6A3, and HSPG2. For clinical translation, we deployed the locked model as an interactive, web-based risk-assessment tool to support early DRN screening and longitudinal monitoring. Cross-ethnic external validation in UK Biobank (n = 502; recruited 2006-2010) reproduced core protein signals and consistent effect directions, confirming robustness across populations. Principal methodological limitation lies in single time point proteomic assessment. CONCLUSION:In this multi-cohort study, we present a proteomics- and ML-based precision prediction system for DRN. Pro-DRN substantially enhanced early risk stratification beyond conventional clinical factors and may support targeted screening and timely neuroprotective interventions, advancing molecularly guided strategies for diabetic eye disease prevention.

PURPOSE:To evaluate the progression rate of severe non-proliferative diabetic retinopathy (sNPDR) in eyes treated with microinvasive pars plana vitrectomy (PPV) versus panretinal photocoagulation (PRP) over 12 months. METHODS:55 eyes of 55 diabetic patients aged >18 years with sNPDR were randomised 1:1 to the PPV group (n=27) or the PRP group (n=28). Standard 25G PPV was performed by an experienced surgeon within 4 weeks of enrolment. Standard PRP was performed in three sessions within 4 weeks of enrolment. The primary outcome was the proportion of eyes progressed from sNPDR to proliferative diabetic retinopathy (PDR) over 12 months. RESULTS:A total of 27 participants (mean (SD) age, 61.19 (8.89) years; 16 male (59.3%)) in the PPV group and 28 participants (mean (SD) age, 60.50 (7.93) years; 11 male (39.3%)) in the PRP group were analysed. At 12 months, no patients in the PPV group progressed to PDR, compared with 2 of 28 patients (7.1%) in the PRP group (p=0.49). The mean (SD) change in total visual field point score was -16.70 (415.23) dB in the PPV group and -314.00 (404.59) dB in the PRP group (p=0.02). For the peripheral 60-4 test, the mean (SD) change was -11.39 (167.99) dB in the PPV group versus -207.05 (308.66) dB in the PRP group (p=0.02). CONCLUSIONS:In patients with sNPDR, PPV and PRP showed no significant difference in PDR progression during the 12-month follow-up, whereas the PPV group preserved better peripheral visual function. TRIAL REGISTRATION NUMBER:NCT04103671.

Purpose To determine whether posterior staphyloma (PS) is associated with long-term trajectories of ocular structural changes, myopia-related complications and visual outcomes in high myopia. Methods This prospective longitudinal cohort study included 614 highly myopic eyes from the Zhongshan High Myopia Cohort Study, followed for up to 12 years. Eyes were categorised by PS status: baseline PS (n=46), new-onset PS (n=94) or no PS (n=474). The associations between PS and myopic macular degeneration (MMD) progression, myopic traction maculopathy (MTM) and plus lesions incidence, longitudinal changes in ocular parameters and incident moderate-to-severe visual impairment (MSVI) were assessed. Results PS was independently associated with increased risks of MMD progression (OR 3.39, 95% CI 1.81 to 6.35, p<0.001), MTM (OR 2.25, 95% CI 1.06 to 4.77, p=0.034) and incident plus lesions (OR 3.15, 95% CI 1.16 to 8.57, p=0.024). The highest risks of MTM and plus lesions were observed in eyes with new-onset PS. Eyes with PS demonstrated significantly faster axial elongation (mean annual rate: baseline PS, 0.120 mm (95% CI 0.099 to 0.142); new-onset PS: 0.129 mm (95% CI 0.114 to 0.145); no PS: 0.066 mm (95% CI 0.060 to 0.073), p<0.001) and a fivefold higher risk of MSVI (95% CI 1.36 to 18.45, p=0.016). Conclusions PS marks a pivotal structural transition in high myopia, identifying a phase of accelerated axial elongation, increased risk of complications and worse visual outcomes, and may serve as a key marker for risk stratification and an important target for early intervention.

Importance:Three-dimensional (3D) eye shape may play a critical role in predicting long-term structural and functional outcomes in high myopia. Objective:To determine whether 3D eye shape subtypes defined by high-resolution magnetic resonance imaging (MRI) predict 15-year structural and functional outcomes in high myopia. Design, Settings, and Participants:This prospective cohort study involved a subsample of individuals with high myopia (spherical equivalent ≤-6.00 D in both eyes) enrolled in the Zhongshan High Myopia Cohort at a single center in China. Participants underwent biennial ophthalmic examinations over 15 years. Baseline assessments began in August 2011, with biennial follow-ups through September 2025. Data were analyzed from October 2025 through December 2025. Exposures:Eye shape was classified into the following 6 categories: spheroidal, ellipsoidal, conical, nasally distorted, temporally distorted, and barrel shaped. Spheroidal and ellipsoidal types were defined as nondeformed and the others as deformed. Main Outcomes and Measures:The primary outcomes were annual axial elongation rate, rapid elongation (≥0.10 mm/y), macular choroidal thinning (subfoveal choroidal thickness <62 µm), progression of myopic macular degeneration (MMD), incidence of posterior staphyloma, visual impairment (best-corrected visual acuity ≤20/40), and visual field defects. Results:Of 190 eyes from 95 participants, 152 eyes completed follow-up and were included in the analysis. Of the 152 eyes analyzed, 77 (50.7%) were from female participants, with an overall mean (SD) age of 32.3 (14.1) years. Baseline shapes included spheroidal (83 eyes [54.6%]), nasally distorted (25 [16.4%]), conical (23 [15.1%]), ellipsoidal (11 [7.2%]), temporally distorted (5 [3.3%]), and barrel shaped (5 [3.3%]). Axial elongation followed a morphology-dependent gradient, from slowest in spheroidal eyes (0.045 mm/y) to fastest in nasally distorted eyes (0.095 mm/y). After multivariable adjustment, nasally distorted eyes elongated by 0.050 mm/y (95% CI, 0.020-0.080 mm/y; P = .001) faster and had higher odds of rapid elongation (odds ratio, 5.74; 95% CI, 1.66-19.82; P = .006). Deformed eyes overall had a 7-fold higher risk of macular choroidal thinning (odds ratio, 7.24; 95% CI, 1.77-29.63; P = .006). Nasally distorted and conical eyes showed the greatest risks for both choroidal thinning and MMD progression. For visual field defects, risk was elevated in nasally distorted and conical eyes. Conclusions and Relevance:Findings from this prospective cohort study suggest that 3D eye shape is an important determinant of long-term outcomes in high myopia. Nasally distorted and conical phenotypes conferred the greatest risks, highlighting the potential value of baseline eye shape stratification for personalized management, risk prediction, or early intervention. Trial Registration:isrctn.org Identifier: ISRCTN56368396.

This study aimed to compare retinal and choroidal circulation and structural parameters between humans and five commonly used experimental animals (rats, mice, guinea pigs, rabbits, and monkeys) using ultra-widefield swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA). The study found that the six species exhibited unique patterns in retinal and choroidal vessel flow distribution. Rats and mice demonstrated significantly higher retinal and choroidal vessel flow density (VFD) compared to humans, while retinal vessels in rabbits are confined to a broad horizontal band, and in guinea pigs are restricted to the peripapillary area. Monkeys displayed retinal vessel flow patterns highly similar to humans, but with a higher vessel flow density in the deep capillary plexus (DCP) within the central region. Retinal and choroidal thicknesses were consistently thinner in rodents and rabbits than in humans, and monkeys displayed a thinner inner retinal layer (IRL) and choroid in the central region. Regarding optic nerve head parameters, both monkeys and rabbits showed smaller optic cup area and rim area compared to humans. However, no significant difference in the cup-to-disc ratio (CDR) was observed between humans and monkeys, whereas rabbits exhibited a significantly higher CDR. These results demonstrate significant interspecies variations in retinal and choroidal circulation, thickness, and optic nerve head structure. The findings provide a reference framework for the careful selection of animal models in ophthalmic research, facilitating a better understanding and application of these models to simulate human ocular diseases.

The repair of corneal damage is essential for maintaining clear vision. Upon corneal epithelial injury, cells at the corneal limbus initiate complex processes such as migration, extracellular matrix remodeling, and proliferation. However, the transcriptional heterogeneity of limbal cell populations during these stages remains understudied. In this study, we used high-throughput long-read single-cell RNA sequencing to analyze five major cell types in the corneal limbus of cynomolgus monkeys at three time points: before injury, and one and three days post-injury. These cell types include terminally differentiated corneal epithelial cells (TDCE), basal cells (BC), transit-amplifying cells (TAC), limbal stem cells (LSC), and conjunctival cells (CC). We identified key regulatory genes and RNA isoforms involved in cell migration, proliferation, and differentiation, including IGF2, FN1, LAMC2, ITGB1, ITGAV, and keratins (KRT3, KRT12, and KRT6A). Our findings reveal the critical roles of LSC and BC in corneal repair and provide new insights into the transcriptional landscape during epithelial healing.

Proteomics offers an unprecedented opportunity to characterize and predict diabetic retinopathy (DR) with minimal invasiveness. Here we examine this in 10,873 individuals with (pre)diabetes from two ethnically distinct cohorts. By simultaneous profiling of ~3000 proteins, we identify 668 associations with mechanistically plausible directionality that constitute a comprehensive DR proteomic landscape with linkages to retinal tomographic structure and genetic predisposition, pointing to established and novel biological pathways conferring DR risk. Integrating DR proteomic profile markedly improves predictive performance beyond clinical and genetic predictors, with plexin B2, growth differentiation factor 15, and renin emerging as top proteins validated across cohorts and linked to retinal microvascular degeneration in Guangzhou Diabetic Eye Study (GDES) based on SS-OCTA. A parsimonious panel of these three proteins alone achieves comparable performance in predicting DR development and progression, while renin is confirmed as a causal promoter through genetic analyses. Our findings highlight the potential of large-scale proteomics in elucidating DR pathogenesis and advancing biomarker discovery, with broad implications for early detection and intervention.

Purpose To investigate the ability to quantify fundus curvature and detect posterior staphyloma using widefield optical coherence tomography (OCT). Design Cross-sectional diagnostic evaluation. Methods This study reviewed 205 highly myopic eyes of 205 participants. The Gaussian curvature map of the fundus was automatically calculated from 2 million scan points over an area of 24 mm x 20 mm, visualizing localized deformations in the posterior region. Two fovea-centered areas were designated as follows: a 6 mm x 6 mm macular region and an 8 mm x 16 mm posterior region. Macular mean curvature, macular curvature deviation, posterior mean curvature, posterior curvature deviation (PCD), and maximum posterior curvature were calculated. The relationship between curvature indices, ocular parameters, and myopic complications was investigated. The diagnostic ability of curvature indices for posterior staphyloma was evaluated. Results The mean (SD) age of 205 participants was 34.06 (12.74) years, with 107 being female (52.2%). Posterior staphyloma was found in 33 of 205 (16.1%) eyes. The curvature value map and curvature deviation map revealed detailed morphologic patterns of posterior staphyloma. Eyes with staphyloma had a steeper and more irregular fundus than eyes without staphyloma, with a larger maximum posterior curvature (20.420 x 10(-3) mm(-2) vs 10.925 x 10(-3) mm(-2), P < .001), posterior mean curvature (6.754 x 10(-3) mm(-2) vs 5.352 x 10(-3) mm(-2), P = .002), macular curvature deviation (1.889 x 10(-3) mm(-2) vs 1.078 x 10(-3) mm(-2), P < .001), and PCD (3.894 x 10(-3) mm(-2) vs 1.683 x 10(-3) mm(-2), P < .001). However, no difference in macular mean curvature was found between eyes with and without posterior staphyloma. Larger maximum posterior curvature, macular curvature deviation, and PCD were associated with greater degrees of myopia, more severe myopic maculopathy, and worse best-corrected visual acuity (all P < .05). PCD demonstrated the ability to discriminate the presence of posterior staphyloma (area under the curve 0.909 [95% CI 0.854-0.963; P < .001]). The optimal cutoff value of PCD was 3.060 x 10(-3) mm(-2) (Youden index = 0.725), with a specificity of 90.7% and a sensitivity of 81.8%. Conclusion Widefield OCT-based analysis of fundus curvature enhances detection and quantitative assessment of posterior staphyloma in high myopia. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

PURPOSE:To compare the progression of myopic maculopathy in patients with stage 3 myopic traction maculopathy (MTM) undergoing either pars plana vitrectomy (PPV) or macular buckling (MB). METHODS:A total of 61 eyes diagnosed with stage 3 MTM were retrospectively divided into two groups: PPV group (30 eyes) and MB group (31 eyes). Best-corrected visual acuity (BCVA), axial length (AL), myopic maculopathy progression, retinal and choroidal thickness were measured and compared. RESULTS:The mean follow-up period was 70.9±13.67 months. The average myopic maculopathy stage in the PPV group progressed from 1.87±0.57 to 2.4±0.72 (P < 0.001). In the MB group, the stage advanced from 2.03±0.66 to 2.1±0.7 (P = 0.5). Progression to a different stage occurred in 14 eyes (46.67%) in the PPV group, compared to only 2 eyes (6.45%) in the MB group. 16.67% of eyes in the PPV group (5 out of 30) and 6.45% of eyes in the MB group (2 out of 31) showed progression within the same MM stage. Additionally, 9 eyes (29.03%) in the MB group exhibited retinal pigment epithelium injury adjacent to the macular buckle ridge (MB-related atrophy). Postoperatively, foveal retinal thickness (197.8±61.53 μm vs. 164.4±49.07 μm, P = 0.02) and central choroidal thickness (81.95±47.7 μm vs. 61.44±50.77 μm, P = 0.032) were significantly greater in the MB group. CONCLUSIONS:For patients with stage 3 MTM, PPV may accelerate the progression of myopic maculopathy, whereas MB may not. Therefore, MB may be a preferable surgical option for these patients.

Photoreceptors are specialized neurons at the core of the retina’s functionality, with optical accessibility and exceptional sensitivity to systemic metabolic stresses. Here we show the ability of risk-free, in vivo photoreceptor assessment as a window into systemic health and identify shared metabolic underpinnings of photoreceptor degeneration and multisystem health outcomes. A thinner photoreceptor layer thickness is significantly associated with an increased risk of future mortality and 13 multisystem diseases, while systematic analyses of circulating metabolomics enable the identification of 109 photoreceptor-related metabolites, which in turn elevate or reduce the risk of these health outcomes. To translate these insights into a practical tool, we developed an artificial intelligence (AI)-driven photoreceptor metabolic window framework and an accompanying interpreter that comprehensively captures the metabolic landscape of photoreceptor–systemic health linkages and simultaneously predicts 16 multisystem health outcomes beyond established approaches while retaining interpretability. Our work, replicated across cohorts of diverse ethnicities, reveals the potential of photoreceptors to inform systemic health and advance a multisystem perspective on human health by revealing eye–body connections and shared metabolic influences. Photoreceptors are specialized neurons of the retina that are sensitive to systemic metabolic stresses. Here, the authors combine in vivo photoreceptor assessment with multisystem health readouts and circulating metabolomics to predict multi-disease risk.

PURPOSE:The study aims to assess the efficacy of integrating macular buckling (MB) with pars plana vitrectomy (PPV), the inverted internal limiting membrane (ILM) flap technique, and air tamponade in treating macular hole retinal detachment (MHRD) in patients with high myopia. METHODS:This retrospective study included sixty-two eyes from sixty-two consecutive patients diagnosed with highly myopic MHRD. The participants were categorized into two groups: the PPV group (n=34) and the combination group (n=28). Best-corrected visual acuity (BCVA), axial length (AL), progression of myopic maculopathy (MM), rates of macular hole (MH) closure and retinal reattachment were assessed and compared. RESULTS:The mean follow-up duration was 14.13±2.57 months. The combination group demonstrated a significant higher rate of MH closure compared to the PPV group (79.41% vs. 100%, P=0.011). Retinal reattachment was successfully achieved in 100% of eyes in the combination group following the initial surgery, in contrast to 70.59% in the PPV group (P=0.002). The combination group demonstrated a significantly greater improvement in BCVA compared to the PPV group (P<0.001). The mean MM stage in the PPV group increased from 2.12±0.69 to 2.38±0.92 (P=0.031). The combination group exhibited no significant progression of MM postoperatively. CONCLUSIONS:The integration of MB with the inverted ILM flap technique and air tamponade seems to enhance both MH closure and retinal reattachment rates, along with notable improvements in BCVA among patients with highly myopic MHRD. Keywords: Macular buckling, Pars plana vitrectomy, Inverted internal limiting membrane flap, Air tamponade, Macular hole retinal detachment.

Myopia progression and its associated complications, which can lead to vision impairment, primarily result from persistent abnormal elongation of the eye's axial length. The previous metabonomic analysis of intraocular fluids suggested intraocular hormones may play a role in high myopia pathogenesis. In this study, significantly reduced concentrations of dehydroepiandrosterone (DHEA) were discovered in the vitreous humor of high myopia eyes. Additionally, DHEA levels in retina tissues of myopic guinea pigs were significantly decreased, further linking intraocular DHEA depletion to myopia-related tissue changes. Recent research has established scleral hypoxia as a fundamental mechanism underlying myopia development, with scleral fibroblasts serving as key functional cells in this process. Thus, this study investigated the effects of DHEA on human scleral fibroblasts under hypoxic conditions to generate novel insights for myopia prevention and treatment. The findings demonstrated that DHEA down-regulates hypoxia-inducible factor 1α (HIF-1α) expression and reduces collagen loss under hypoxic conditions. Additionally, DHEA reversed the decreased cell proliferation observed in human scleral fibroblasts in vitro. These effects appear to be mediated through changes in mitochondrial dynamics and regulation of BNIP3L-mediated mitophagy induced by DHEA under hypoxia. The results suggest DHEA represents a promising novel therapeutic strategy for preventing myopia development.

Myopia presents a noteworthy global health concern, urging exploration of innovative treatments. The role of intraocular pressure (IOP) in regulating the progression of myopia has been controversial. To investigate the impact of reducing IOP to varying extents on myopia progression, three groups receiving distinct IOP-lowering medications (Brinzolamide, Latanoprost, and a combination of Brinzolamide and Latanoprost) were designed in a form-deprived myopic guinea pig model. Additionally, proteomics analyses were conducted to identify differentially expressed proteins in the sclera. Based on 24-h and 4-week IOP monitoring, the group receiving both Brinzolamide and Latanoprost exhibited the greatest magnitude of IOP reduction and the most significant inhibition of axial length (AL) growth. Moreover, the administration of IOP-lowering medications increased choroidal thickness and induced alterations in the structure of scleral collagen fibrils. Notably, scleral proteomics revealed remodeling processes associated with key mechanisms, including proteolysis, fibrinolysis, and metal ion binding. Our findings highlight that pressure-dependent scleral remodeling contributes to the deceleration of AL elongation. These results underscore the efficacy of IOP reduction in mitigating the progression of myopia, providing a promising alternative strategy for myopia management.

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.

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.