眼科领域文献阅读汇编

To evaluate the association between baseline optical coherence tomography (OCT) biomarkers and 2-year disease progression from intermediate age-related macular degeneration (iAMD) to advanced atrophic AMD, defined by OCT, with emphasis on ellipsoid zone (EZ) attenuation/loss and other quantitative structural features. Retrospective cohort study. 502 eyes with iAMD and no evidence of atrophy (i.e., RPE loss with associated outer retinal atrophy) or exudation at baseline, each with 2-year follow-up OCT imaging. Baseline and 2-year spectral-domain OCT scans were analyzed using a validated, machine learning-enhanced multilayer segmentation platform with subsequent certified reader review and correction. Quantitative OCT parameters included EZ-RPE thickness, partial and total EZ attenuation, drusen volume, hyperreflective foci (HRF) count, total RPE loss, and outer nuclear layer-RPE (ONL-RPE) thickness. Fully automated deep-learning models quantified hypertransmission and EZ at-risk (i.e., a model developed to identify areas of abnormal EZ-RPE thinning in the absence of RPE loss). A random forest classifier was trained using baseline features, with performance assessed using 5-fold stratified cross-validation. Development of OCT-defined advanced atrophic AMD defined by total RPE loss with associated outer retinal atrophy with an area ≥0.05 mm2 (i.e., cRORA equivalent) at 2 years and baseline OCT biomarkers associated with progression. Eyes that developed advanced atrophic AMD showed significantly greater partial and total EZ attenuation, reduced EZ-RPE and ONL-RPE thickness, higher drusen volume, and greater HRF counts than non-converters (all p<0.05). Deep-learning-derived EZ at-risk and hypertransmission metrics were also significantly higher in converters. The cross-validated predictive model incorporating all baseline features achieved a mean area-under-the-ROC curve (AUC) of 0.85 ± 0.02. EZ integrity metrics and HRF count ranked as the most influential predictors of progression. Quantitative OCT biomarkers, particularly EZ integrity measures and HRF count, are strongly associated with 2-year progression to advanced atrophic AMD in iAMD. These findings support the role of quantitative EZ integrity metrics and hyperreflective foci features for early disease risk stratification and may inform the design of prevention-focused or early-intervention clinical trials aimed at delaying the onset of atrophic changes.

Lactate was once regarded merely as a byproduct of glycolysis, but is now recognized as a multifunctional metabolite that coordinates energy redistribution, intercellular communication, receptor-mediated signaling, and epigenetic regulation. In the retina, these functions are especially consequential because visual processing depends on a highly specialized and energetically demanding tissue, characterized by steep oxygen gradients, a dual vascular supply, and tightly integrated metabolic crosstalk among photoreceptors (PCs), Müller glia, the retinal pigment epithelium, vascular cells, and retinal ganglion cells. In this review, we synthesize current advances in lactate signaling and lactylation in the retina, and examine how their dysregulation contributes to neovascularization, inflammation, and neurodegeneration in disorders including diabetic retinopathy, age-related macular degeneration, autoimmune uveitis and glaucoma. Drawing from these metabolic insights, therapeutic interventions targeting lactate signaling and lactylation are discussed as potential approaches to mitigate retinal abnormalities. Collectively, this review highlights the central importance of lactate signaling and lactylation in retinal physiology and pathology, and provides a conceptual framework for developing metabolic interventions aimed at restoring retinal lactate homeostasis.

Current anti-VEGF monotherapies for neovascular age-related macular degeneration (AMD) and diabetic retinopathy (DR) are limited by incomplete therapeutic responses, drug resistance, and the high burden of frequent intravitreal injections (IVTs). Although extensive research is underway to improve therapeutic outcomes, there remains a critical need for more effective strategies. To address this limitation, a bicistronic rAAV8 vector, Afb/cAng1, was developed to co-express aflibercept (Afb) and COMP-Ang1 (cAng1), simultaneously inhibiting VEGF signaling and activating the Tie2 pathway. In vitro characterization using conditioned medium containing secreted Afb/cAng1 showed that the treatment effectively suppresses VEGF-induced VEGFR2 phosphorylation to below basal levels while robustly activating Tie2. Consequently, the conditioned medium significantly inhibited endothelial cell migration and tube formation, and restored VE-cadherin expression compromised by VEGF stimulation or hyperglycemic conditions. Afb/cAng1 in a 3D angiogenesis-on-a-chip model reduces neovascular area and vascular permeability, showing superior efficacy compared to Afb (Eylea). In vivo choroidal neovascularization (CNV) analysis confirmed dose-dependent anti-angiogenic efficacy of rAAV8-Afb/cAng1, comparable to that of Eylea. These findings highlight Afb/cAng1 as a dual-targeting gene therapy strategy that concurrently suppresses pathological angiogenesis and promotes vascular stabilization through coordinated VEGF inhibition and Tie2 activation in AMD and DR.

Leukocyte cell-derived chemotaxin 2 (LECT2), a newly discovered hepatokine involved in immunomodulation and inflammatory processes, has recently been implicated in diabetic retinopathy pathogenesis. However, the specific role and mechanism of LECT2 in diabetic retinopathy remain largely unclear. A publicly available liquid biopsy proteomics dataset was reanalysed and validated using retinal samples from individuals with diabetic retinopathy. A LECT2-knockdown (Lect2+/-) mouse model of diabetic retinopathy was established to evaluate the role of LECT2 in vivo. Retinal pathology was assessed by Periodic Acid-Schiff staining and H&E staining, and LECT2 expression was assessed by western blotting. In parallel, a high glucose (HG)-induced human Müller cell model was used to investigate the subcellular localisation and functional effects of LECT2. LECT2 expression and inflammatory signalling were analysed following LECT2 knockdown or overexpression, and its nucleus-cytoplasm distribution was examined by fractionation assays. The interaction between LECT2 and ribosomal protein S27a (RPS27A) was characterised by immunoprecipitation-MS, co-immunoprecipitation, molecular docking and split-GFP assays, followed by RPS27A silencing to assess its effects on inflammatory protein expression. Proteomic reanalysis of proliferative diabetic retinopathy liquid biopsy data identified 1479 upregulated proteins, with chemotaxis among the most significantly enriched Gene Ontology terms (false discovery rate <0.001). Among 17 chemotaxis-related candidate proteins, LECT2 emerged as a potential regulator of diabetes-associated inflammation, a finding further supported by its elevated expression in the retinas of individuals with diabetic retinopathy. In diabetic Lect2+/- mice, LECT2 deficiency aggravated retinal microvascular injury and inflammatory responses. LECT2 was predominantly expressed in retinal Müller cells, implicating it in glia-associated retinal inflammation. In HG-treated human retinal Müller cells, RPS27A was identified as a downstream target of LECT2 and was upregulated under hyperglycaemic conditions. Mechanistically, HG stimulation increased the expression and nuclear accumulation of both LECT2 and RPS27A. LECT2 interacted with RPS27A at the Lys48 site, promoting its nuclear retention and limiting its cytoplasmic translocation. This, in turn, inhibited IκBα ubiquitination and degradation, thereby suppressing NF-κB-driven inflammatory signalling. Taken together, our studies indicated the protective role of LECT2 in diabetes-induced dysfunction of retinal Müller cells, supporting the feasibility of targeting LECT2 in the management of diabetic inflammation and microvasculopathy.

Age-related macular degeneration (AMD) is a complex disease wherein age, genetics, and environment play a role. How each of these factors contribute to the overall disease initiation and progression remains largely unelucidated. A renewed examination of the existing literature regarding the blood supply to the outer retina may provide novel insights. Hypoxia in the retinal pigment epithelium (RPE) can produce features of AMD, including photoreceptor degeneration. In the macula, the choriocapillaris has unique features making it susceptible to hypoperfusion, producing low-grade ischemia and chronic tissue hypoxia. The choriocapillaris experiences vascular loss and decreased blood flow early in AMD. Genetic risk, when viewed through a new lens, points to vascular insult as central to AMD pathophysiology. Complement-related risk genes are active in the vasculature, from large tributary vessels to small vessels of the choriocapillaris. HtrA serine peptidase 1 (HTRA1) is associated with cerebral small vessel disease and localizes to the choriocapillaris in AMD. Ageing can be interpreted as inevitable atherosclerosis from large to small vessels of the cerebral system. Western diets, smoking, and a rising prevalence of metabolic syndrome in people over age 60 are confirmed to accelerate both atherosclerosis and AMD. A perfusion-based model for complement-related, soft drusen-associated AMD is proposed while also explaining a second phenotype of non-complement related subretinal drusenoid deposit-associated AMD. Common to both phenotypes of AMD is chronic hypoperfusion causing decreased oxygen exchange and waste removal at the neurovascular unit of the choriocapillaris, RPE, and photoreceptors. Understanding AMD as an end-organ vascular disease may move us towards a unifying hypothesis.

Current research on pathological retinal neovascularization primarily focuses on growth factors, inflammation, and endothelial signaling pathways. However, increasing attention is being directed toward disruptions in the retinal immune microenvironment. Therefore, deciphering the immune-angiogenic interplay could uncover therapeutic avenues for neovascular disorders. Through integrative analyses of single-cell RNA sequencing from human fibrovascular membranes and multicohort clinical datasets, we identified neutrophil infiltration as an independent risk factor for diabetic retinopathy progression. Mechanistically, activated microglia preceded and potentiated neutrophil infiltration by secreting galectin-3 (GAL3), establishing a self-amplifying feedback loop that sustained microglial activation and drove pathological angiogenesis in mice with oxygen-induced retinopathy (OIR). To therapeutically disrupt this loop, we engineered a photocurable hydrogel for the sustained intravitreal delivery of GAL3 and vascular endothelial growth factor (VEGF)-neutralizing antibodies, which effectively suppressed aberrant angiogenesis in mice with OIR. Together, these findings reinforce the concept of retinal neovascularization as an immunovascular disorder and underscore the therapeutic potential of microenvironment-modulating strategies using biomaterials.

Blinding diseases due to the degeneration of photoreceptors (PhRs), such as geographic atrophy (GA) secondary to dry age-related macular degeneration and retinitis pigmentosa (RP), leave the rest of the retinal circuitry largely intact, albeit unable to respond to light. Gene therapy has been able to revert PhR degeneration, but it can be applied only to a rare mutation affecting a small subset of RP patients. Alternatively, implanted electronic retinal prostheses aim at a larger population by electrically stimulating surviving neurons. However, the treatment is invasive and costly and provides limited resolution. Photopharmacology can develop photoswitchable small molecules to restore vision impairment by conferring light sensitivity to ion channels that are widely expressed in the remaining inner retinal neurons, and a first-in-human clinical trial is ongoing. Here, we have developed novel photoswitchable small-molecule ligands of metabotropic glutamate 6 (mGlu6) receptors, which are located exclusively at the dendrites of ON bipolar cells (postsynaptic to PhRs) and can leverage a privileged position to mimic physiological signals in the remnant retinal circuit. These photoswitchable ligands (prosthe6) thus act as "molecular prostheses" that can restore the light input to the retina via upstream-targeted control of the circuit after PhR degeneration. Prosthe6 compounds are allosteric, drug-like, water-soluble, and display outstanding in vitro properties including full efficacy, nanomolar potency, fast deactivation in ambient white light, and fast reactivation in the dark. In vivo experiments show that they readily recover the saccadic eye movements of blinded zebrafish larvae and restore the innate light-avoidance behavior in the mouse models of blindness (GA and RP). These effects are mediated by mGlu6 receptors in vivo. In addition, at least two compounds (prosthe6-12 and -15) can restore sight by topical administration and display promising safety properties to become potential drug candidates for sight restoration in patients with degenerative blinding diseases.

Sensitization to birch pollen is a major contributor to allergic rhinitis in Europe, with sensitization rates in many countries from 10% to 20% of the general population. Growing evidence suggests that air pollution enhances the allergenicity of pollen; however, the clinical consequences of this co-exposure remain poorly understood. This study investigated whether air pollution intensifies birch pollen allergenicity and assessed its effects on symptom severity and basophil activation in allergic and non-allergic individuals. Fifty birch-allergic patients and twenty-five non-atopic controls were examined over two consecutive pollen seasons (2023-2024). Daily nasal, ocular, and asthma symptoms were recorded using a mobile application. Ambient air pollutants (PM2.5, PM10, and O3) and birch pollen concentrations were continuously monitored in Kraków. Basophil activation tests (BAT) were performed using commercial birch pollen extracts, Bet v1 allergen, and natural pollen collected from highly and less polluted areas. Basophil activation was quantified by CD63 expression using flow cytometry. Asthmatic symptoms showed significant positive correlations with both birch pollen and PM concentrations (p < 0.05), especially in 2023. Pollen collected from polluted sites induced significantly stronger basophil activation compared with pollen from less polluted areas (p < 0.0001). The magnitude of basophil activation correlated with serum IgE levels to birch and Bet v 1, as well as with clinical symptom scores. Air pollution enhances the allergenic potency of birch pollen, resulting in heightened basophil activation and more severe allergic symptoms. These findings highlight the importance of integrating air pollution monitoring alongside pollen surveillance when assessing allergic disease burden and evaluating the effectiveness of allergen immunotherapy.

Retinal vasculitis is a sight-threatening condition associated with diverse ocular and systemic diseases. Variability in terminology and definitions across clinical practice and research has limited diagnostic consistency, communication among specialists, and comparability of studies. To develop standardized, consensus-based definitions for retinal vasculitis and related terms to improve diagnostic clarity and harmonize communication among ophthalmologists and other medical specialties. This was an international modified Delphi consensus study conducted using a structured consensus process guided by a comprehensive literature review, including systematic reviews and meta-analyses. Two rounds of Delphi surveys were performed, and consensus was predefined as at least 75% agreement. Included was an international expert panel of 27 specialists in ophthalmology, rheumatology, pathology, imaging, and research methodology. The specialists had recognized expertise in retinal and systemic vasculitis, retinal imaging, or consensus methodology. Study data were analyzed from March to September 2025. Participation in a structured Delphi process evaluating proposed definitions and terminology related to retinal vasculitis and associated vascular inflammatory entities. Consensus definitions for retinal vasculitis and related entities, with agreement using predefined consensus thresholds. A total of 27 international experts participated in the Delphi process. After 5 executive committee members involved in developing preliminary definitions were excluded from voting to minimize bias, a total of 22 independent experts completed both Delphi rounds. All candidate statements exceeded the predefined consensus threshold in the first round (agreement range, 83.3%-95.5%), although some demonstrated variability in the strength of agreement. After refinement of definitions, consensus strengthened in the second round, with agreement levels ranging from 95.2% to 100%. The panel established consensus definitions for 8 terms: retinal vasculitis, vascular leakage, infectious retinal vasculitis, noninfectious retinal vasculitis, retinal perivasculitis, retinal vasculopathy, primary retinal vasculitis, and far-peripheral vascular leakage. These definitions were developed to distinguish vascular leakage from true vasculitis, clarify inflammatory and noninflammatory vascular disorders, and promote consistent terminology across clinical practice and research. This international Delphi consensus established standardized nomenclature for retinal vasculitis and related vascular inflammatory entities. Adoption of these definitions may improve diagnostic accuracy, facilitate interpretation of imaging findings, enhance consistency across clinical studies, and support future research efforts, including the development of artificial intelligence-based classification systems for retinal vascular disease.

To evaluate the association of neurodevelopmental disorders (NDDs) and behavioral disorders with amblyopia, myopia, strabismus, and strabismus surgery rates. Retrospective cohort study. Children aged ≤18 years with and without NDDs or behavioral disorders identified in a nationwide multicenter federated electronic health record network. Children diagnosed with attention-deficit/hyperactivity disorder, autism spectrum disorder, learning disorders, conduct disorder, or oppositional defiant disorder between 2013 and 2025 were compared with children without NDDs or behavioral disorders. Propensity score matching (1:1) was performed using demographics, medical comorbidities, laboratory values, and healthcare utilization metrics. After matching, time-to-event analyses were conducted using Kaplan-Meier estimation and Cox proportional hazards models, with prespecified sensitivity and negative control analyses. Disorder-specific analyses and exploratory analyses of strabismus surgery rates among children with strabismus or strabismic amblyopia were also performed. Hazard ratios (HRs) with 95% confidence intervals (CIs) for amblyopia, myopia, and strabismus derived from propensity score-matched cohorts. The primary analysis included 1,429,440 children with NDDs or behavioral disorders and 3,522,241 controls, yielding 1,156,503 matched pairs. Baseline characteristics were well-balanced after matching. Children with NDDs or behavioral disorders had an increased risk of amblyopia (HR: 1.60; 95% CI: 1.45-1.79), strabismus (HR: 1.66; 95% CI: 1.57-1.71), and myopia (HR: 1.55; 95% CI: 1.45-1.70) compared with controls following the initial diagnosis of an NDD or behavioral disorder (all P < 0.001). Increased risk was also observed across clinically relevant disease subtypes, individual disorders, and multiple follow-up intervals (all P < 0.001). Children with NDDs or behavioral disorders underwent strabismus surgery less frequently than controls (19.2% vs. 28.4%; P < 0.001). NDDs and behavioral disorders were associated with increased risk of amblyopia, myopia, and strabismus across multiple follow-up intervals, disease subtypes, and individual disorders. Pediatric eye disease may represent an important component of the overall health burden in this population. These findings support heightened clinical awareness and developmentally appropriate vision screening strategies in children with NDDs or behavioral disorders. Lower rates of strabismus surgery in this population warrant further investigation.

To compare the accuracy of vertical cup-disc ratios (VCDR), ascertained by machine learning (ML) versus human graders, from fundus images for glaucoma detection. This study utilizes population-based data, with a disease prevalence and case-mix that is closer to a real-world setting than conventional case-control studies, with the aim of developing improved glaucoma screening tests. Cross-sectional analysis of a population-based study. 6,304 participants of the EPIC-Norfolk Eye Study with color fundus images gradable by humans and ML in both eyes. VCDR was independently estimated from two-dimensional fundus images of EPIC-Norfolk Eye Study participants by trained human graders (H-VCDR) and an externally trained, open access, ML model (ML-VCDR). A neural network trained on 81,830 ophthalmologist-labeled images was used to generate pseudo-labels for over 100,000 UK Biobank images, on which ML-VCDR was subsequently trained. Glaucoma status was ascertained by tertiary center specialist examination. Predictive performance of VCDR for glaucoma status was examined using logistic regression. ML-VCDR estimates were additionally compared to a popular open-source ML model (AutoMorph) and scanning laser ophthalmoscopy (Heidelberg Retinal Tomography (HRT)). Area Under the Receiver Operated Characteristic Curve (AUROC), explained variance (McFadden's pseudo-R2). Of 6,304 participants (mean age 68 years; 57% women), 696 had glaucoma or suspect status in at least one eye. For left eyes, H-VCDR and ML-VCDR explained 17% (95% CI 14.7 - 20.4) and 31% (95% CI 27.9 - 33.9) of glaucoma status variance and had an area under the ROC curve (AUROC) of 79% (95% CI 76.8 - 81.2) and 88% (95% CI 86.3 - 89.1), respectively. Right eye H-VCDR and ML-VCDR explained 20% (95% CI 16.9 - 22.6) and 35% (95% CI 32.4 - 37.9) of the variance, and had an AUROC of 81% (95% CI 78.6 - 82.5) and 90% (95% CI 88.7 - 91.0), respectively. ML-VCDR also performed better than AutoMorph and HRT at predicting glaucoma status from VCDR estimations. In this population-based setting, ML far outperformed trained human graders at predicting specialist-ascertained glaucoma status from fundus images. This provides promise for ML-supported strategies for glaucoma population screening.

Nanoparticulate drug delivery systems represent a promising platform for sustained intraocular drug release following intravitreal administration, leveraging low metabolic turnover of the vitreous to maintain therapeutic drug levels over extended periods. Despite this potential, nanoparticle diffusion toward the visual axis can induce light scattering and visual disturbance. Given the negative charge of the vitreous, surface-engineered nanoparticles provide a strategy to modulate particle mobility and restrict off-target migration. Here, we performed a 6-week in vivo evaluation in pigs of an intravitreally applied, positively charged, cyclic-arginine surface-functionalized liposomal nanocarrier designed to reduce intravitreal mobility. Three formulations containing 0.1%, 0.5%, or 1% cyclic-arginine-modified phospholipid were compared with unmodified control liposomes in a large animal pig model. A multimodal biocompatibility and performance assessment was conducted, including intraocular pressure monitoring, fundus imaging, structural and angiographic OCT, dye-based angiography, and post-mortem retinal immunostainings. Cyclic-arginine surface functionalization of the liposomes resulted in a concentration-dependent reduction in intravitreal mobility, quantified by vitreous haze and fundus-based distribution analyses. All surface-engineered nanoparticles demonstrated excellent ocular biocompatibility without structural or vascular adverse effects. These data establish cyclic-arginine surface modification as a robust design principle to modulate intravitreal mobility and support the development of next-generation nanoparticle biomaterials for long-acting ophthalmic drug delivery.

CDHR1 is a recently identified cause of autosomal recessive retinal degeneration manifesting as three distinct clinical phenotypes: macular dystrophy, cone-rod dystrophy or retinitis pigmentosa. In this review, we summarise the discovery and characterisation of CDHR1, clinical phenotypes, natural history and therapeutic approaches including gene supplementation and CRISPR gene editing. CDHR1 is a non-classical cadherin that is highly expressed in cone and rod photoreceptors and is essential for the higher-order organisation of the functionally critical outer segments. Promising pre-clinical data show that AAV gene supplementation therapy delivered by subretinal injection can lead to long-term morphological, structural, functional and behavioural improvements in the Cdhr1 knockout mouse model. Notably, CDHR1 supplementation restored full-length photoreceptor outer segments that are usually shortened and disorganised in disease models and prolonged photoreceptor survival - key mechanisms for the functional and behavioural rescue effects that were observed. The disease is likely to be underdiagnosed because CDHR1-associated macular dystrophy - likely to be the most common disease phenotype - is most often caused by a 'silent' nucleotide substitution that has previously been overlooked by genetic testing. Since the macular dystrophy phenotype has phenotypic similarities to advanced dry age-related macular degeneration (AMD), misdiagnoses are common. CDHR1-associated macular dystrophy also shares phenotypic features with a variety of monogenic masquerades such as ABCA4, PRPH2 and GUCY2D-associated macular dystrophies; we present a flowchart to guide the clinical distinction of these disorders which is now critical for patients as their treatments diverge. AAV gene therapy may be beneficial across the CDHR1 disease spectrum - including those with hypomorphic variants associated with macular dystrophy or retinitis pigmentosa. The coding sequence fits into AAV and with the macular dystrophy phenotype, there is a large time window for potential intervention and a large treatable population. Hence clinical trials are anticipated. It is therefore important that patients with CDHR1-associated retinal degeneration are accurately phenotyped and genetically confirmed to support the application of CDHR1 gene therapy.

Programmable gene activation has broad therapeutic potential but remains constrained by the large effector size, limited multiplexing capacity, and challenges in in vivo delivery. Here, we develop the TIGR-TasR-mediated activator (TIGRa), a compact transcriptional activator derived from the tandem interspaced guide RNA (TIGR)-TIGR-associated protein (TasR) system that is mechanistically distinct from CRISPR-based activators. TIGRa is less than half the size of dSpCas9-based activators while achieving comparable or greater activation efficiency. Its native TIGR array architecture enables efficient multiplexed regulation, supporting simultaneous activation of up to 12 endogenous genes from a single compact construct. TIGRa-mediated multi-gene activation efficiently reprogrammed human fibroblasts into induced pluripotent stem cells. In addition, an all-in-one adeno-associated virus (AAV)-TIGRa vector activated endogenous CaMKII in vivo, promoting retinal ganglion cell survival and preserving visual function in a mouse model of N-methyl-D-aspartic (NMDA)-induced retinal injury. These results establish TIGRa as a compact and multiplexable platform for therapeutic gene regulation and in vivo genetic medicine.

To investigate the efficacy and safety of a novel dual-sided composite defocus (DSCD) lens for pediatric myopia control. Prospective, randomized, double-masked, three-arm, parallel-controlled clinical trial with 1-year follow-up. A total of 225 children aged 6-14 years with myopia ranging from -0.50 D to -6.00 D were randomized 1:1:1 to DSCD, single-surface defocus (SSD), or single-vision spectacle (SVS) lenses. Overall, 194 participants (86.2%) completed the 1-year follow-up. Participants were randomly assigned to the DSCD, SSD, or SVS lens group. The DSCD lens incorporated a front-surface microlens array and a posterior freeform aspheric design intended to generate an asymmetric peripheral myopic defocus profile. Outcomes were measured at baseline and during the 12-month follow-up. Statistical analyses included analysis of covariance, Pearson correlation, and exploratory subgroup analyses. The primary outcomes were 12-month changes in axial length (AL) and spherical equivalent refraction (SER). At 12 months, the DSCD group exhibited significantly less SER progression than the SVS group (-0.22 ± 0.37 D vs -0.83 ± 0.47 D; P < 0.001) and the SSD group (-0.22 ± 0.37 D vs -0.45 ± 0.43 D; P = 0.005). Axial elongation was also significantly slower with DSCD than with SVS lenses (0.19 ± 0.14 mm vs 0.42 ± 0.18 mm; P < 0.001). No statistically significant difference in axial elongation was observed between the DSCD and SSD groups. The DSCD lens reduced SER progression by 73.6% and AL elongation by 55.2% relative to SVS lenses. Exploratory subgroup analyses suggested less progression in children aged 8-12 years, those with baseline AL of 24-25 mm, and those with low myopia. No lens-related adverse events were observed, and all groups demonstrated high compliance and good adaptation. Over 12 months, DSCD lenses resulted in significantly less SER progression and axial elongation than SVS lenses. Compared with the SSD lenses tested in this study, DSCD lenses showed significantly less SER progression, whereas the difference in axial elongation was not statistically significant. DSCD lenses were generally well tolerated and may represent a spectacle-based option for pediatric myopia control.

Pseudomonas aeruginosa (P. aeruginosa) keratitis can progress rapidly to vision-threatening disease, even with intensive therapy. Virulence-associated genes are key determinants of ocular-surface pathogenesis. We therefore sought to develop a composite wbp-exo genotyping framework for risk stratification and to guide wbp-dependent, LPS-directed, levofloxacin-polymyxin B (LVX-POL) combination therapy for high-risk corneal infections. A well-characterised clinical P. aeruginosa keratitis cohort was integrated with whole-genome sequencing. Based on comprehensive virulence-gene identification and annotation, the relationship between strain-level genetic features and clinical prognosis was analysed. The differences between WBP1 strains and WBP2 strains in adhesion, invasion, and biofilm formation in corneal epithelial cells were further evaluated. To establish biological plausibility, wbp genotypes were correlated with LPS O-antigen electrophoretic profiles and in vivo corneal inflammatory phenotypes in murine infection, including the observation of leucocyte recruitment and cytokine responses. To further confirm the key role of wbp gene status and LPS O-antigen in pathogenicity, wbpL knockout and reconstitution strains were constructed. Their appearances in vitro and in vivo were evaluated. Finally, a mechanistic rationale for an LPS-directed LVX-POL regimen was tested in a high-risk WBP1 P. aeruginosa murine keratitis. Whole-genome sequencing was performed on 46 clinical P. aeruginosa isolates and identified an average of 332 virulence- and fitness-associated genes per strain. The exo and wbp gene families were significantly associated with patient prognosis. A fusion model (AUC = 0.86) outperformed single-gene-family models (EXO: 0.66; WBP: 0.72) for predicting clinical outcomes. Intact wbp cassettes were enriched in poor-outcome isolates, and electrophoretic LPS profiles indicated that WBP1 strains produce highly polymerised O-antigen associated with sustained neutrophil recruitment and cytokine production. Murine experiments further implicated wbp genes in clinical pathogenesis, showing stronger immune responses and higher expression of TLR4, MyD88, TRAF6, p65, p-p65, IL-6, TNF-α, and IL-1β throughout the inflammatory course. After knocking out wbpL gene, the WBP1 strain got stronger in biofilm formation and adhesion but weaker in inflammation and ocular surface survival. In the high-risk WBP1 P. aeruginosa keratitis model, LVX-POL combinations achieved complete ulcer resolution and markedly improved stromal infiltration and hypopyon, outperforming LVX monotherapy. The wbp gene family was identified as a key genetic factor that contributes to the LPS O-antigen structure, inflammatory intensity, bacterial ocular surface survival and poor prognosis in P. aeruginosa keratitis. A WBP1-targeted, LPS-directed LVX-POL regimen was proposed as a mechanistically informed option for high-risk strains. This research was supported by Beijing Public Health High-level Talent Training Program (Phase III-03-14), Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project (2026ZD01909300) and Beijing Natural Science Foundation "QiYan" Undergraduate Research Fund (QY26496).

First: to determine whether the cup-to-disc ratio (CDR) of patients with GLP-1 RA associated nonarteritic anterior ischemic optic neuropathy (NAION) is similar to the CDR of NAION patients without GLP-1 RA exposure. Second: to stratify the odds of developing NAION based on CDR. A retrospective, multi-center, case control study of the CDR of NAION cases diagnosed between 2018-2024 SUBJECTS AND CONTROLS: The Disc-at-Risk Study Group included 16 neuro-ophthalmology centers that reviewed medical records of 1,812 unaffected fellow eyes from 2,169 consecutive patients with NAION. The control group included both eyes of 465 patients. The study compared the unaffected fellow eyes of three groups of NAION patients: semaglutide users (117 eyes), non-semaglutide GLP-1 RA users (83 eyes) and no GLP-1 RA medications (1,612 eyes). Control eyes defined the distribution of CDR in the general population. CDR of unaffected fellow eyes of NAION patients with and without exposure to GLP-1 RA medications RESULTS: The average provider-estimated CDR in unaffected fellow eyes of NAION patients was 0.13 with no significant difference among the three groups. A measured CDR ≤ 0.40 was found in 94% of fellow eyes but only 56% of controls (p<0.001). A measured CDR ≤ 0.20 was found in 54% of fellow eye photographs but only 9% of controls (p<0.001). Eyes with a measured CDR ≤ 0.20 have the highest NAION odds (OR=46.3; 95% CI 23.0-93.4), and eyes with a CDR >0.20 and ≤ 0.40 had more modest odds (OR=6.8; 95% CI 3.5-13.2) compared with eyes with a measured CDR >0.40. NAION patients with and without exposure to GLP-1 RA medications have the same high prevalence of crowded optic discs. The odds of NAION are inversely proportional to CDR. Irrespective of GLP-1 RA exposure, eyes with a photo-measured CDR ≤ 0.20 have 46 times greater odds of NAION than eyes with a CDR > 0.40. Although the absolute risk of NAION is low, this quantification of NAION risk may help better inform patients concerned about NAION risk. This study does not assess whether GLP-1 RA medications are an independent risk factor for NAION.