AIM: To investigate the genetic basis of Weill-Marchesani syndrome (WMS) in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations. METHODS: Comprehensive clinical assessments and genetic analyses were performed on a Chinese family with two affected siblings. Whole-exome sequencing (WES) was conducted for the proband and other family members. Bioinformatics tools were used to evaluate the conservation, predicted pathogenicity, and structural effects of the identified ADAMTS17 variants. In addition, protein structure modeling was applied to assess the functional impacts of the mutations. RESULTS: The proband (a 32-year-old male) and his elder sister (42y) presented typical clinical features of WMS, including short stature, brachydactyly, high myopia, ectopia lentis, and secondary glaucoma. WES identified a novel compound heterozygous mutation in ADAMTS17: a splicing mutation (c.451-2A>G) inherited from the father and a missense mutation (c.1043G>A; p.C348Y) inherited from the mother. The splicing mutation disrupted normal mRNA splicing and processing, leading to premature translation termination. The missense mutation, which is located in the metalloprotease catalytic domain, was predicted to abolish a critical disulfide bond, thereby impairing protein stability. Both mutations exhibited high evolutionary conservation and were predicted to be pathogenic by multiple bioinformatics algorithms. CONCLUSION: A novel compound heterozygous mutation in ADAMTS17 is identified in this WMS-affected Chinese family, and its pathogenicity is verified via bioinformatics analysis and protein structural modeling. These findings are expected to facilitate the genetic diagnosis of WMS and deepen the understanding of its molecular pathogenesis.

AIMS:Vascular endothelial growth factor (VEGF) drives corneal neovascularization (CorNV), yet no anti-VEGF eye drops are clinically available. We report phase I/IIa trials of KH906, a novel topical anti-VEGF agent. METHODS:Trial 1 was a phase I, open-label, dose-escalation study in healthy adults receiving KH906 at 0.1, 0.5, or 1.0 mg/mL. Trial 2 was a phase I, multicentre, open-label, dose-escalation study in patients with CorNV at the same doses. Trial 3 was a phase IIa, randomized, double-masked, placebo-controlled study assigning patients 1:1:1 to 0.5 mg/mL KH906, 1.0 mg/mL KH906, or placebo. Primary endpoints were safety, tolerability and pharmacokinetics (Trials 1 and 2) and safety, tolerability and efficacy (Trial 3). RESULTS:From 10 December 2018 to 16 June 2021, 18 healthy participants and 39 patients with CorNV were enrolled. One treatment-related adverse event occurred: a mild corneal epithelial defect in the 1.0-mg/mL group in Trial 3. No serious or other drug-related adverse events were observed. In Trial 2, KH906 reduced the CorNV area and vessel length. In Trial 3, at Day 28, mean changes in CorNV area were -1.2 (0.8), -1.6 (1.1) and -0.7 (1.1), and mean changes in CorNV length were -8.0 (7.3), -6.6 (5.9) and -1.7 (7.9), in the 0.5-mg/mL KH906, 1.0-mg/mL KH906 and placebo groups, respectively. The 1.0-mg/mL dose produced greater reduction of the CorNV area than lower doses, indicating a dose-response effect. CONCLUSIONS:KH906 appears safe and well tolerated and demonstrates preliminary efficacy in reducing CorNV, with higher doses showing greater effect, supporting further clinical development.

Skin wound infection is a key factor that hinders the healing process and repair outcome of wounds, especially when it involves drug-resistant bacteria, which is extremely difficult to eliminate. Therefore, developing wound dressings with the ability to kill drug-resistant bacteria holds great value. Herein, carboxymethyl chitosan (CMCS) and 2,4,6-trihydroxybenzaldehyde (THBA)@silver ion chelates were assembled into a triple dynamically cross-linked hydrogel (CTA) through imine bonds, hydrogen bonds, and polyphenol metal chelate bonds. The CTA0.15 hydrogel exhibits sensitive near-infrared response properties. When exposed to 808 nm near-infrared light with a power density of 0.3 W/cm2, the temperature can easily rise to between 45 °C and 50 °C, enabling photothermal sterilization. Combined with the strong antibacterial activity of silver ions and the photothermal effect of the hydrogel, it can quickly (15 min) and completely eliminate common pathogenic bacteria (E. coli and S. aureus) and drug-resistant bacteria (MRSA) in vitro. In addition, this hydrogel also possesses injectability, tissue adhesiveness, self-healing property, shape adaptability, antioxidant capability, catalase (CAT)-like activity, and biocompatibility. The in vivo experiments and transcriptome analysis demonstrated that the combination of CTA hydrogel and NIR treatment significantly accelerated the healing process of MRSA-infected wounds by eliminating antibiotic-resistant bacterial infections, regulating inflammatory responses, promoting collagen deposition and angiogenesis.

BACKGROUND:Dry eye disease (DED) commonly impairs quality of life. This phase 3, randomized, double-masked, multicenter, vehicle-controlled trial evaluated the efficacy of 5.0% lifitegrast ophthalmic solution (KH732) in improving signs and symptoms of DED. METHODS:Adults with moderate-to-severe DED and corneal staining score ≥2.0 in any corneal region were randomized 1:1 to lifitegrast (KH732) or vehicle twice daily for 84 days after a 3-7-day vehicle washout. The primary endpoint was change from baseline in inferior corneal staining score (ICSS) at Day 84. Secondary endpoints included changes in total corneal staining score, Eye Dryness Score (EDS), Ocular Surface Disease Index (OSDI), 7-item visual analogue scale, and Ocular Discomfort Score. RESULTS:At Day 84, lifitegrast (n = 309) significantly reduced ICSS versus vehicle (n = 306) (P = 0.027). In a post hoc analysis, the effect was more pronounced in participants with the highest baseline staining in the inferior region (P = 0.046). Lifitegrast also significantly improved EDS (adjusted P = 0.006), ocular discomfort (adjusted P = 0.010), photophobia (adjusted P = 0.004), and OSDI (adjusted P = 0.014) versus vehicle. Post hoc analyses showed significant between-group differences in EDS, photophobia, and OSDI as early as Day 14. No serious ocular adverse events were reported. CONCLUSIONS:Lifitegrast (KH732) improved both signs and symptoms of DED and was generally well tolerated, with potentially greater benefit in patients with prominent inferior corneal staining.

Suction loss is a small-incision lenticule extraction (SMILE) surgery complication which may compromise postoperative visual quality. Most instances of intraoperative suction loss can be promptly remedied; however, the reports of two consecutive suction losses leading to an incomplete procedure are limited. In the present case report a 24-year-old man underwent SMILE at the General Hospital of Ningxia Medical University (Yinchuan, China); the surgery was successfully completed in the right eye, nevertheless, the left eye experienced two consecutive suction losses, resulting in incomplete treatment. At ~1.5 months post operation, the patient presented to The First Affiliated Hospital of Xi'an Jiaotong University (Xi'an, China) where the treating physicians were unaware of the exact details of the first procedure. At that time, the uncorrected distance visual acuity in the left eye was 20/400, and the corrected distance visual acuity was 20/16. Subsequently, the patient received femtosecond laser-assisted in situ keratomileusis surgery for the left eye. At the 1-month postoperative visit, the uncorrected distance visual acuity had improved to 20/13. The present case demonstrates that suction loss carries a certain probability (0.17-5.06%) during SMILE, with two consecutive intraoperative suction losses being even more uncommon; however, with remedial measures, favorable postoperative visual outcomes can be secured.

Background:Preoperative corneal astigmatism is prevalent among cataract patients and has a negative effect on uncorrected distance visual acuity. Toric IOLs are commonly used to correct astigmatism and clinical trials and expert consensus have reported advantages as compared to non-toric IOLs, but the degree and the consistency of these improvements remain to be more clearly defined. Methods:Clinical studies comparing toric and non-toric IOL implantation in cataract patients with corneal astigmatism were identified in PubMed and Web of Science. The primary outcome was postoperative residual refractive astigmatism; secondary outcomes were UDVA, corrected distance visual acuity, the proportion of eyes with residual refractive cylinder ≤ 0.5 D, and postoperative spherical equivalent. Effect estimates were pooled as standardized mean differences, mean differences or odds ratios along with 95% confidence intervals. Results:A total of twelve studies qualified for inclusion. Toric IOLs yielded lower residual refractive astigmatism (SMD = -1.03, 95% CI -1.16 to -0.90) and better UDVA (SMD = -0.91, 95% CI -1.07 to -0.76) than non-toric IOLs. More eyes with toric IOLs achieved residual cylinder ≤ 0.5 D (OR = 3.31, 95% CI 2.44 to 4.48). The differences in spherical equivalent were small (MD = 0.07 D, 95% CI 0.02 to 0.13) and are likely to be of limited clinical relevance. Conclusions:In patients with corneal astigmatism, toric IOLs provide more precise astigmatic correction and better uncorrected distance vision. These pooled effect sizes refine the current consensus and may assist refractive planning in cataract surgery.

PURPOSE:The development of the avascular lens depends on tightly regulated epithelial proliferation, differentiation into elongated fiber cells, and organelle elimination to maintain long-term transparency. Although Adenosine triphosphate (ATP) ectonucleotidases and Purinergic Receptors have been implicated in tissue morphogenesis, their specific contributions to lens development remain unclear. This study aimed to characterize the spatiotemporal expression patterns and predictive associations of ATP signaling components during lens development. METHODS:Transcriptomic datasets from human, mouse, and chicken lenses were analyzed to map the spatiotemporal expression of ATP ectonucleotidases and purinergic receptors. Pathway enrichment and correlation analyses with key developmental genes were performed to explore their functional associations. In vitro experiments were conducted using HLE‑B3 cells and primary embryonic chick lens cultures to assess cell viability, proliferation, apoptosis, and differentiation under ATP manipulation and pharmacological P2 receptor blockade. RESULTS:Transcriptomic profiling revealed region- and stage-specific expression of ATP ectonucleotidases and purinergic receptors, which were functionally linked to calcium signaling, autophagy, FGFR pathways, and glutathione-dependent redox regulation. In vitro, ATP exerted biphasic effects on HLE-B3 cells: low concentrations enhanced cell viability, whereas high concentrations increased epithelial-mesenchymal transition (EMT)-associated gene expression. In embryonic chick lens cultures, depletion of extracellular ATP or inhibition of P2 receptors reduced expression of key differentiation markers. CONCLUSION:Integrated bioinformatic and experimental evidence indicate that ATP signaling components display distinct spatiotemporal expression patterns and possible associations with multiple functional pathways. In addition, various purinergic receptor subtypes may be implicated in coordinated and potentially diverse processes during lens development and the maintenance of transparency. Together, these correlative findings provide insights into the involvement of ATP and purinergic signaling in lens morphogenesis and homeostasis.

The eye, a complex organ essential for visual perception, is composed of diverse cell populations with specialized functions; however, the complex interplay between these cellular components and their underlying molecular mechanisms remains largely elusive. Traditional biotechnologies, such as bulk RNA sequencing and in vitro models, are limited in capturing cellular heterogeneity or accurately mimicking the complexity of human ophthalmic diseases. The advent of single-cell RNA sequencing (scRNA-seq) has revolutionized ocular research by enabling high-resolution analysis at the single-cell level, uncovering cellular heterogeneity, and identifying disease-specific gene profiles. In this review, we provide a review of scRNA-seq application advancement in ocular physiology and pathology, highlighting its role in elucidating the molecular mechanisms of various ocular diseases, including myopia, ocular surface and corneal diseases, glaucoma, uveitis, retinal diseases, and ocular tumors. By providing novel insights into cellular diversity, gene expression dynamics, and cell–cell interactions, scRNA-seq has facilitated the identification of novel biomarkers and therapeutic targets, and the further integration of scRNA-seq with other omics technologies holds promise for deepening our understanding of ocular health and diseases.

PURPOSE:Increasing epidemiologic evidence has indicated that PM2.5 exposure is strongly correlated with the prevalence of allergic conjunctivitis (AC), but there is no experimental model for elucidating the underlying mechanism involved. We established a stable PM2.5-induced mouse model of AC to explore the adverse effects of PM2.5 on the ocular surfaces and the underlying mechanisms involved. METHODS:BALB/c mice were sensitized by intraplanar injection of 200 μg PM2.5 on day 0 and challenged for 10 consecutive days, beginning on day 9, with eye drops containing 12.5 mg/mL PM2.5. Assessments of the ocular surfaces, eye blink counts, and tear secretion were performed to evaluate clinical symptoms. The whole eyes were harvested for histopathological and immunofluorescence analyses, the conjunctiva was isolated for Western blotting, and the sera were subjected to IgE ELISA to evaluate the immune characteristics and TSLP-related pathway expression. Furthermore, mouse bone marrow-derived macrophages (BMDMs) were incubated with 25 μg/mL PM2.5 for 24 h. Cellular protein and RNA were extracted for Western blotting and RNA sequencing. RESULTS:PM2.5 exposure induced clinical manifestations and pathological changes similar to those in human AC. The sensitization and challenge evoked Th2 responses and serum IgE production. PM2.5 exposure mediated TSLP production in macrophages and aggravated allergic inflammation through the TSLP-TSLPR and TSLP-OX40L signaling pathways in vivo. Macrophages produced TSLP and polarized to the M1 phenotype after PM2.5 administration in vitro. CONCLUSIONS:These results demonstrate a reproducible method for establishing a PM2.5-induced AC model. In addition, PM2.5 exposure stimulated macrophages to secrete TSLP and enhance allergic inflammation.

PURPOSE:To explore the characteristics of corneal biomechanical parameters and corneal thickness in different corneal regions in progressive keratoconus treated by accelerated "epithelium off" cross-linking (A-CXL) surgery. METHODS:This is a retrospective study and is self-controlled before and after surgery. A total of 39 eyes of 25 patients with progressive keratoconus were recruited and treated by A-CXL. The corneal biomechanical parameters and corneal thickness were recorded at baseline, 1-month, 3-month, and 6-month after surgery. Besides, analysis of correlations was applied to explore the association between these two features. RESULTS:Most of the biomechanical parameters, corneal thickness of different areas, as well as visual acuity, curvature and higher-order aberrations (HOAs), showed significant changes at 1 month and 3 months after surgery. Then gradually became stable and close to baseline values at 6 months postoperative. The epithelium became thicker earlier (after 1 month). The central and inferior areas of corneal stroma and the whole cornea were significantly thinnest at 3 months, other areas were thinnest at 1 month. Only several biomechanical parameters showed positive or negative correlations with corneal thickness, including the changes of them from baseline to different time after treatment. CONCLUSION:The accelerated cross-linking not only has a significant effect, especially on the corneal central, inferotemporal, and inferonasal regions, which can prevent the progression of keratoconus. But also, can maintain the integrity of the epithelium, achieve corneal biomechanical recovery and improve visual acuity, curvature and HOAs in the short term at the same time.

Aims To investigate the shared genetic mechanisms between type 2 diabetes (T2D) and primary open-angle glaucoma (POAG). Using large-scale genome-wide association study (GWAS) data, we performed single nucleotide polymorphism (SNP) level analysis to detect pleiotropic variants and loci, paired eQTL mapping analysis and gene-level analysis to identify candidate pleiotropic genes. In addition, Mendelian randomisation (MR) analysis was performed to assess causal associations.Materials and methods We used POAG GWAS data from Finngen (9565 cases and 430 250 controls) and T2D GWAS data from 55 555 European ancestry samples. We used Linkage Disequilibrium SCore (LDSC) regression to assess the genetic association between T2D and POAG and further used PLeiotropic Analysis under the COmposite null hypothesis (PLACO) to identify shared genetic variants between paired traits. Finally, we further used MR analysis to explore the causal association between T2D and POAG at the genetic level.Results The LDSC results and MR analysis revealed that the T2D effect was significantly higher than that of the POAG (OR=1.09, 95% CI 1.03 to 1.14, p=1.50×10−3). The PLACO property analysis determined that the T2D sum POAG shared 178 individual SNPs, separate localisation of 79 individual causes. The five most popular choices are based on the effectiveness of CCND2, SVEP1, ST6GAL1, TCF7L2 and HMGA2. expression quantitative trait loci mapping further revealed 36 genes with regulatory roles in optic nerve-related brain tissues. Functional enrichment analyses indicated that these pleiotropic genes are involved in neurodevelopmental, neuroprotective and metabolic pathways, with tissue-specific enrichment observed in neural, pancreatic, adipose and retinal tissues. It is possible to present the main comorbid mechanisms of T2D and POAG.Conclusions Our study provides new insights into the aetiology and pathogenesis of T2D and POAG at the genetic level.

Background: Retinoblastoma (RB) is the most common primary intraocular malignancy in children, primarily caused by inactivation of the RB1 tumor suppressor gene. Despite advancements in multimodal therapies, the molecular mechanisms underlying RB progression and its tumor microenvironment (TME) remain poorly understood, limiting the development of effective targeted treatments.Methods: This study integrates bulk and single-cell RNA sequencing data to characterize the molecular landscape of RB. Differential gene expression analysis, pathway enrichment analysis, and single-sample gene set enrichment analysis (ssGSEA) were performed to uncover key pathways and immune cell populations. Immune checkpoint molecules, m6A RNA modification-related genes, and ferroptosis-associated genes were analyzed to identify potential therapeutic targets. Protein-protein interaction (PPI) networks and cell-cell communication analyses were conducted to explore intercellular signaling within the TME. Additionally, functional validation was performed for CDKN1A, a candidate gene identified from transcriptomic analysis, using shRNA-mediated knockdown and in vitro assays.Results: Transcriptomic profiling revealed distinct gene expression signatures between RB and normal retinal tissues, including upregulation of oncogenic pathways (e.g., MYC targets and G2/M checkpoint regulation) and downregulation of tumor suppressor pathways (e.g., p53 signaling). Chemotherapy-induced gene expression changes were observed, notably the activation of immune-related pathways such as antigen presentation and NK cell-mediated cytotoxicity. Immune checkpoint molecules (PDCD1, CD274, HAVCR2) exhibited cell-type-specific expression, indicating potential for immunotherapy. Elevated expression of m6A regulators (METTL3, WTAP) and ferroptosis-associated genes (ACSL4, SLC7A11) pointed to novel therapeutic vulnerabilities. Among key regulatory genes, CDKN1A was identified as significantly downregulated in RB. Functional experiments demonstrated that knockdown of CDKN1A inhibited cell proliferation and induced G1 phase arrest in RB cell lines, supporting its potential tumor-promoting role in this context.Conclusion: This study provides a comprehensive molecular and cellular overview of RB progression and reveals novel therapeutic targets, including immune checkpoints, m6A modification enzymes, ferroptosis regulators, and CDKN1A. Our findings emphasize the need to address tumor heterogeneity and cell-type-specific gene expression in designing effective personalized therapies for RB patients.

PURPOSE:To evaluate and contrast the effectiveness and safety of two conbercept treatment protocols-a three-dose treat-and-extend (3+T&E) regimen and a three-dose pro re nata (3+PRN) regimen-in Chinese patients diagnosed with neovascular age-related macular degeneration (nAMD). METHODS:Eligible patients, who had not undergone anti-VEGF intraocular injections within 3 months prior to enrollment, were randomly assigned to either the 3+T&E or 3+PRN regimen. The 3+T&E group received at least three monthly injections, with subsequent visit intervals extended based on disease activity assessment. The primary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to week 48, using a predefined noninferiority threshold. RESULTS:Among 501 participants (249 in 3+T&E, 252 in 3+PRN), approximately half had prior anti-VEGF treatment. At 48 weeks, both regimens showed significant BCVA improvements (+9.9 for 3+PRN, +8.6 for 3+T&E; p = .208), with comparable rates of ≥15-letter gains (32.12% for 3+PRN, 30.77% for 3+T&E; p = .827). The 3+PRN group received fewer injections (mean 6.4 vs. 6.9 in 3+T&E; p = .028) but had shorter intervals between injections (6.93 weeks vs. 7.46 weeks in 3+T&E; p = .010). Drug-related adverse events occurred in 5% of patients, with ocular events evenly distributed and minimal cardiovascular events reported. CONCLUSION:Both 3+T&E and 3+PRN conbercept regimens effectively improved visual and anatomical outcomes in Chinese nAMD patients. The 3+T&E regimen was noninferior to 3+PRN in improving BCVA from baseline to week 48. The 3+T&E regimen enabled longer injection intervals while 3+PRN regimen with less injections is more cost-effective while maintaining a comparable safety profile. Treatment plan tailored to an individual patient's situation appears necessary.

BACKGROUND:To investigate the prevalence and correction of anisometropia among primary school children in northwestern China. METHODS:A cross-sectional school-based study was conducted in Shaanxi Province. Visual acuity (VA) and autorefraction without cycloplegia were assessed in all participants, and some received axial length (AL) measurements. Anisometropia was categorised based on spherical equivalent (SE), cylindrical (CYL), and AL. The prevalence of anisometropia and refractive correction across different ages and sexes, and correlations between ocular parameters, were analysed. RESULTS:The study included 29 153 children aged 6-12 (mean age 9.52 ± 1.73 years) for VA and autorefraction measurements, and 1176 children for AL measurements. The prevalence of myopia (SE ≤ -0.50 D), hyperopia (SE ≥ +0.50 D), and anisometropia (interocular SE difference ≥1.00 D) was 65.26%, 15.09%, and 16.50%, respectively. Anisometropia severity, based on SE (χ2 = 443.758, p < 0.001), CYL (χ2 = 41.669, p < 0.001), and AL (χ2 = 95.505, p < 0.001), increased with age, with no significant differences between sexes. Interocular SE difference correlated with interocular spherical power (r = 0.806, p < 0.001), CYL (r = 0.21, p < 0.001), and AL (r = 0.365, p < 0.001). Additionally, interocular CYL difference was positively correlated with interocular AL difference (r = 0.16, p < 0.001). Despite the high prevalence of anisometropia, less than 30% of affected children received refractive correction. CONCLUSIONS:Anisometropia of SE, CYL, and AL increased progressively with age. Despite the elevated prevalence of anisometropia, the utilisation of refractive correction remained strikingly low.

Abstract Background Retinal ischemia/reperfusion (IR) injury is a common pathological process in many ophthalmic diseases. Interleukin-1β (IL-1β) is an important inflammatory factor involved in the pathology of retinal IR injury, but the mechanism by which IL-1β is regulated in such injury remains unclear. Caspase-11 non-canonical inflammasomes can regulate the synthesis and secretion of IL-1β, but its role in retinal IR injury has not been elucidated. This study aimed to evaluate the role of caspase-11 non-canonical inflammasomes in retinal IR injury. Methods Retinal IR injury was induced in C57BL/6J mice by increasing the intraocular pressure to 110 mmHg for 60 min. The post-injury changes in retinal morphology and function and in IL-1β expression were compared between caspase-11 gene knockout (caspase-11−/−) mice and wild-type (WT) mice. Morphological and functional changes were evaluated using hematoxylin–eosin staining and retinal whole mount staining and using electroretinography (ERG), respectively. IL-1β expression in the retina was measured using enzyme-linked immunosorbent assay (ELISA). The levels of caspase-11-related protein were measured using western blot analysis. The location of caspase-11 in the retina was determined via immunofluorescence staining. Mouse type I astrocytes C8-D1A cells were used to validate the effects of caspase-11 simulation via hypoxia in vitro. Small-interfering RNA targeting caspase-11 was constructed. Cell viability was evaluated using the MTT assay. IL-1β expression in supernatant and cell lysate was measured using ELISA. The levels of caspase-11-related protein were measured using western blot analysis. Results Retinal ganglion cell death and retinal edema were more ameliorated, and the ERG b-wave amplitude was better after retinal IR injury in caspase-11−/− mice than in WT mice. Further, caspase-11−/− mice showed lower protein expressions of IL-1β, cleaved caspase-1, and gasdermin D (GSDMD) in the retina after retinal IR injury. Caspase-11 protein was expressed in retinal glial cells, and caspase-11 knockdown played a protective role against hypoxia in C8-D1A cells. The expression levels of IL-1β, cleaved caspase-1, and GSDMD were inhibited after hypoxia in the si-caspase-11 constructed cells. Conclusions Retinal IR injury activates caspase-11 non-canonical inflammasomes in glial cells of the retina. This results in increased protein levels of GSDMD and IL-1β and leads to damage in the inner layer of the retina.

PURPOSE:To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN:Randomized, double-masked, multicenter, active-controlled, noninferiority phase II study. PARTICIPANTS:A total of 231 treatment-naive and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled. METHODS:Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa, or 2 mg aflibercept groups. Participants in all groups received 3 initial monthly loading doses, followed by treatment every 8 weeks, with assessment every 4 weeks up to week 52. MAIN OUTCOME MEASURES:The primary end point was the mean best-corrected visual acuity (BCVA) change from baseline to week 36. The prespecified noninferiority margin was set as -5 letters (80% confidence interval [CI]). RESULTS:Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, and +12.0 letters, respectively; least squares mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups. CONCLUSIONS:Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile. FINANCIAL DISCLOSURE(S):The author(s) have no proprietary or commercial interest in any materials discussed in this article.

BackgroundGrowing evidence emphasizes the importance of xanthophyll carotenoids and omega-3 fatty acids in eye health. However, the beneficial effects of such supplementation have not been thoroughly discussed among adults with high screen exposure. Current trial evidence on lutein bioavailability is contradictory, and the interactions of dietary intervention with host-related factors remain elusive. This study aims to investigate the comparative effectiveness of supplementation with macular xanthophylls and omega-3 fatty acids on macular pigment optical density (MPOD) and visual function, access the bioavailability of free lutein and lutein ester, and explore the complex interplay between genetic variations, intestinal microbiota, and the dietary intervention in Chinese adults with long-term exposure to digital devices.MethodsThe Lutein, Zeaxanthin, and Omega-3 (LZO) clinical trial is a 24-week multicenter, randomized, double-blind, placebo-controlled trial of 600 participants recruited from research centers, universities, and communities. Individuals are eligible to participate if they are aged over 18 years and use digital devices for over 8 h daily in the last 2 years, and will be randomized to six arms. A total of three visits will be scheduled at baseline, 12 and 24 weeks. The primary outcome is the change in MPOD over the 24-week intervention. The secondary outcomes are changes in visual function (visual acuity, best-corrected visual acuity, contrast and glare sensitivity, critical flicker fusion, reaction time, visuognosis persistence, symptoms and signs of dry eye, retinal thickness, and optical quality), and changes in serum lutein and zeaxanthin concentrations, and erythrocyte membrane omega-3 fatty acids. Genetic variations will be determined using genome-wide genotyping at baseline. 16S rRNA gene sequencing will be utilized to assess microbiome compositional changes before and after intervention.DiscussionThe trial is anticipated to establish early interventions to prevent photochemical ocular damage and delay the onset of vision impairment in young adults with long-term repeated exposure to screen-based electronic devices, and provide valuable insights for the development of precision nutrition strategies for maintaining eye health.Clinical trial registrationwww.clinicaltrials.in.th, Identifier, TCTR20220904002.