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Cholinergic Improvement of Low-Flow Segmental Aqueous Humor Outflow in Humans 人类低流量段性房水流出的胆碱能改善
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2026-01-09 DOI: 10.1016/j.xops.2026.101070
Alex S. Huang MD, PhD , Mary Anne Garner PhD , Mark E. Clark MEng , Lindsay A. Rhodes MD , Martin Kallab MD, PhD , Hao F. Zhang PhD , Robert N. Weinreb MD , Clemens A. Strohmaier MD, PhD , Christopher A. Girkin MD

Purpose

To evaluate the influence of pharmacologic cholinergic stimulation on segmental aqueous humor outflow (AHO) in living human eyes of brain-dead organ donors.

Design

A prospective, nonrandomized, and interventional study.

Subjects

Brain-dead organ donors.

Methods

Aqueous angiography (AA) was performed using intracameral indocyanine green (ICG; 0.4%) in brain-dead organ donors to establish baseline segmental high-flow and low-flow (LF) AHO regions. The eyes were then treated using intracameral balanced salt solution (BSS; n = 5) or Miochol-E (n = 7; 10 mg/ml), which is US Food and Drug Administration-approved acetylcholine. Repeat AA was then performed using intracameral fluorescein (2%). Aqueous angiography images were acquired using a FLEX Spectralis (Heidelberg Engineering). Aqueous humor outflow signal intensity was quantified per quadrant or per eye in a masked fashion and compared across conditions.

Main Outcome Measures

Aqueous angiography fluorescent patterns, baseline AA signal intensity in various quadrants, and change in AA signal intensity after drug treatment or control.

Results

All eyes received initial baseline ICG AA. Segmental AHO was seen qualitatively and quantitatively across all quadrants (temporal: 18.4 ± 10.0; superior: 25.6 ± 16.5; nasal: 49.9 ± 28.6; and inferior: 25.9 ± 13.2 arbitrary units [AU], mean ± standard deviation). Consistent with prior reports, the greatest AHO was seen nasally (temporal vs nasal, P < 0.001; superior vs. nasal, P = 0.012; and inferior vs nasal, P = 0.013). After BSS treatment, fluorescein AA showed very similar patterns to baseline ICG AA. After Miochol-E treatment, fluorescein AA showed qualitative AHO improvement in some baseline LF regions. After drug treatment, Miochol-E-treated eyes showed a greater quantitative increase in fluorescence intensity per quadrant (25.9 ± 31.7 AU; P < 0.001) and per eye (25.9 ± 22.9; P = 0.024) compared to the BSS control condition.

Conclusions

Cholinergic stimulation enhances AHO in segmental regions as opposed to circumferentially around the limbus. In particular, focal improvement in baseline LF regions was observed, implying a segmental response to drug treatment. Understanding the biological and physiological basis underlying this responsiveness may lead to new pharmacological and surgical glaucoma treatments.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
目的探讨药理学胆碱能刺激对脑死亡器官供者活体眼段性房水流出(ho)的影响。设计一项前瞻性、非随机、干预性研究。实验对象:脑死亡的器官捐献者。方法对脑死亡器官供者采用胞内吲哚菁绿(ICG; 0.4%)进行水样血管造影(AA),建立基线分段高流量和低流量(LF) who区域。然后用眼内平衡盐溶液(BSS; n = 5)或miocholl - e (n = 7; 10 mg/ml)治疗眼睛,这是美国食品和药物管理局批准的乙酰胆碱。然后用囊内荧光素(2%)进行重复AA。使用FLEX Spectralis (Heidelberg Engineering)获得水血管造影图像。房水流出信号强度在每个象限或每只眼睛被量化,并在不同条件下进行比较。主要观察指标:水相血管造影荧光模式、各象限基线AA信号强度、药物治疗或对照后AA信号强度的变化。结果所有眼均接受初始基线ICG AA。在所有象限(颞:18.4±10.0;上:25.6±16.5;鼻:49.9±28.6;下:25.9±13.2任意单位[AU],平均值±标准差)中定性和定量地观察到部分who。与先前的报告一致,最大的who见于鼻部(颞部vs鼻部,P < 0.001;上鼻部vs上鼻部,P = 0.012;下鼻部vs下鼻部,P = 0.013)。BSS治疗后,荧光素AA显示出与基线ICG AA非常相似的模式。经过micocholo - e治疗后,荧光素AA在一些基线LF区域显示出质的改善。药物治疗后,与BSS对照组相比,miocholl - e治疗组每象限荧光强度(25.9±31.7 AU; P < 0.001)和每只眼荧光强度(25.9±22.9;P = 0.024)有更大的定量增加。结论能量刺激可增强脑缘周围部分区域的ho。特别是,观察到基线LF区域的局灶性改善,这意味着对药物治疗有部分反应。了解这种反应的生物学和生理学基础可能会导致新的药物和手术治疗青光眼。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。
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引用次数: 0
Determining Genetic Cause of Posterior Staphylomas in Eyes with Pathologic Myopia by Whole Exome Sequencing 通过全外显子组测序确定病理性近视眼后葡萄肿的遗传原因
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2026-01-05 DOI: 10.1016/j.xops.2025.101058
Ziye Wang MD , Changyu Chen MD, PhD , Yijin Wu MD , Yuki Nagata PhD , Toshihiro Tanaka MD, PhD , Shiqi Xie MD, PhD , Hongshuang Lu MD, PhD , Yining Wang MD , Jianping Xiong MD, PhD , Liwen Zhang MD , Koju Kamoi MD, PhD , Kyoko Ohno-Matsui MD, PhD
<div><h3>Purpose</h3><div>To identify genetic variants in posterior staphylomas in eyes with pathologic myopia using whole exome sequencing and to determine possible molecular mechanisms contributing to the pathogenesis.</div></div><div><h3>Design</h3><div>An observational, case-control study.</div></div><div><h3>Participants</h3><div>Two hundred sixty-four unrelated Japanese patients with myopia (≤ –0.50 diopters) and posterior staphyloma, which was diagnosed by ultra-widefield OCT, 3-dimensional magnetic resonance imaging, and Optos imaging.</div></div><div><h3>Methods</h3><div>Whole exome sequencing was performed on genomic DNA from peripheral blood. After variant filtering, the allelic frequencies were compared with control data obtained from East Asian subsets of the 1000 Genomes Project Phase III, the Exome Aggregation Consortium, and the Japanese Multi-Omics Reference Panel using Fisher exact test. A gene panel was constructed based on 13 staphyloma-associated disorders. Variants showing significant frequency differences (<em>P</em> ≤ 0.05) and an overlap of the gene panel were analyzed using gene set enrichment analysis with the DAVID Knowledgebase (v2023q4). Protein–protein interaction analysis was performed to assess functional associations.</div></div><div><h3>Main Outcome Measures</h3><div>The statistically associated variants and genes, gene set enrichment analysis results, protein–protein interaction networks, and involvement of basement membrane structures, including the inner limiting membrane (ILM) and Bruch membrane, were studied.</div></div><div><h3>Results</h3><div>Whole exome sequencing identified 16 656 missense variants in 8628 genes. Comparative allele frequency analyses with public databases revealed 3925 variants that had significantly higher allelic frequencies in the subjects. Of these, 81 genes overlapped with a curated staphyloma-related gene panel and were subjected to gene set enrichment analysis. The findings showed enrichment in basement membrane, extracellular matrix, and collagen-related pathways. The <em>COL4A5, COL18A1, COL2A1</em>, and <em>COL9A3</em> genes are concurrently enriched across these pathways. A missense variant in <em>COL4A5</em> was identified in 27 patients, and 96.3% of whom were females. Protein–protein interaction analysis demonstrated functional connections among these 4 genes.</div></div><div><h3>Conclusions</h3><div>Variants in the <em>COL4A5, COL18A1, COL2A1, and COL9A3</em> genes probably contribute to the pathogenesis of a posterior staphyloma through the disruption of collagen synthesis and basement membrane integrity. This was especially effective for the ILM and Bruch membrane. The <em>COL4A5</em> variant may cause an ocular-predominant phenotype in heterozygous female carriers, independent of the classical features of Alport syndrome.</div></div><div><h3>Financial Disclosure(s)</h3><div>The authors have no proprietary or commercial interest in any materials discussed in this artic
目的利用全外显子组测序技术鉴定病理性近视眼后葡萄肿的遗传变异,探讨其可能的发病机制。设计:观察性病例对照研究。研究对象:日本近视(≤-0.50屈光度)合并后葡萄肿患者264例,经超宽视场OCT、三维磁共振成像和Optos成像诊断。方法对外周血基因组DNA进行全外显子组测序。变异过滤后,使用Fisher精确检验将等位基因频率与来自1000基因组计划第三期东亚亚群、外显子组聚集联盟和日本多组学参考小组的对照数据进行比较。基于13种葡萄球菌相关疾病构建了基因面板。使用DAVID知识库(v2023q4)进行基因集富集分析,分析频率差异显著(P≤0.05)和基因面板重叠的变异。进行蛋白-蛋白相互作用分析以评估功能关联。研究了统计相关的变异和基因、基因集富集分析结果、蛋白质-蛋白质相互作用网络以及包括内限制膜(ILM)和布鲁赫膜在内的基底膜结构的参与。结果8628个基因的全外显子组测序鉴定出16 656个错义变异。与公共数据库的比较等位基因频率分析显示,受试者中有3925个等位基因频率显著较高的变体。其中,81个基因与葡萄球菌相关基因组重叠,并进行基因集富集分析。结果显示在基底膜、细胞外基质和胶原相关通路中富集。COL4A5、COL18A1、COL2A1和COL9A3基因在这些通路中同时富集。在27例患者中发现COL4A5错义变异,其中96.3%为女性。蛋白互作分析证实了这4个基因之间的功能联系。结论COL4A5、COL18A1、COL2A1和COL9A3基因的变异可能通过破坏胶原合成和基底膜完整性参与后葡萄肿的发病机制。这对ILM和Bruch膜特别有效。COL4A5变异可能在杂合子女性携带者中引起眼显性表型,独立于Alport综合征的经典特征。作者在本文中讨论的任何材料中没有专有或商业利益。
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引用次数: 0
Cover 封面
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.xops.2025.101044
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引用次数: 0
Re: Hiraoka et al: Quantitative Mapping of Posterior Eye Curvature in Children Using Distortion-Corrected OCT: Insights into Temporal Region Morphology 回复:hiroka等人:使用扭曲校正OCT定量绘制儿童后眼曲率:颞区形态学的见解
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-12-29 DOI: 10.1016/j.xops.2025.101040
Nianjia Wang , Xindi Liu , Liang Yao
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引用次数: 0
The CFH–CFHR5 Locus in Wet Age-Related Macular Degeneration, Polypoidal Choroidal Vasculopathy, and Central Serous Chorioretinopathy 湿性年龄相关性黄斑变性、息肉样脉络膜血管病变和中枢性浆液性脉络膜视网膜病变中的CFH-CFHR5位点
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-12-24 DOI: 10.1016/j.xops.2025.101043
Zhen Ji Chen PhD , Jun Yu MMed , Mary Ho MSc , Danny S.C. Ng MPH , Marten E. Brelen PhD , Alvin L. Young MMedSc , Jason C.S. Yam MD , Clement C. Tham BM, BCh , Chi Pui Pang DPhil , Li Jia Chen PhD
<div><h3>Purpose</h3><div>To evaluate the effects of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement factor H–complement factor H related 5 (<em>CFH</em>–<em>CFHR5</em>) locus on neovascular age-related macular degeneration (nAMD), polypoidal choroidal vasculopathy (PCV), and chronic central serous chorioretinopathy (cCSCR) in Chinese patients.</div></div><div><h3>Design</h3><div>Case-control genetic association study.</div></div><div><h3>Participants</h3><div>A total of 846 patients (341 nAMD, 288 PCV, and 217 cCSCR including 43 with secondary macular neovascularization [MNV]) and 632 healthy Chinese controls.</div></div><div><h3>Methods</h3><div>A total of 17 candidate SNPs were initially selected from the <em>CFH–CFHR5</em> region; after excluding 5 SNPs that deviated from Hardy–Weinberg equilibrium, 12 SNPs were retained for the final analysis. Association analyses included logistic regression adjusted for age and sex and haplotype-based analysis using Haploview. Study-wide significance threshold was set at <em>P</em> < 0.0042 for allelic tests (Bonferroni-corrected for 12 SNPs) and at <em>P</em> < 0.05 for haplotype tests (adjusted using 10 000 permutations).</div></div><div><h3>Main Outcome Measures</h3><div>Associations between individual SNPs and haplotypes in the <em>CFH</em>–<em>CFHR5</em> locus with nAMD, PCV, and cCSCR (with or without MNV), respectively.</div></div><div><h3>Results</h3><div>The tagging SNP, rs12144939, for the <em>CFHR3/1</em> deletion was significantly associated with nAMD (odds ratio [OR] = 0.37, <em>P</em> = 0.0031). Notably, we identified 3 candidate variants showing novel associations with PCV, including rs12144939 (OR = 0.29, <em>P</em> = 6.29 × 10<sup>–4</sup>), rs423641 in <em>CFHR1</em> (OR = 0.74, <em>P</em> = 0.0038), and rs10922152 in <em>CFHR5</em> (OR = 1.55, <em>P</em> = 0.0031). No SNP in this locus was associated with cCSCR without MNV, whereas <em>CFH</em> rs529825 was nominally associated with cCSCR with MNV (OR = 0.47, <em>P</em> = 0.0047). Similar patterns of haplotype associations were observed across the 3 maculopathies. Notably, the haplotype A-T-C-G spanning <em>CFHR4</em>, <em>CFHR2,</em> and <em>CFHR5</em> (OR = 1.81, permutation <em>P</em> = 0.0099) and haplotype G-A-G within <em>CFHR5</em> (OR = 1.56, permutation <em>P</em> = 0.025) were specifically associated with PCV.</div></div><div><h3>Conclusions</h3><div>This study validates the association of the <em>CFHR3/1</em> deletion (tagged by rs12144939) with nAMD. Furthermore, we reveal a novel genetic architecture for PCV within the <em>CFH</em>–<em>CFHR5</em> locus, characterized by associations at rs12144939, rs423641 (<em>CFHR1</em>), and rs10922152 (<em>CFHR5</em>), as well as risk haplotypes unique to PCV. These findings underscore the critical role of <em>CFH</em>-related genes in PCV and provide new insights into its genetic mechanisms.</div></div><div><h3>Financial Disclosures</h3><div>The author h
目的探讨补体因子H -补体因子H相关5 (CFH-CFHR5)基因座单倍型标记单核苷酸多态性(snp)在中国新生血管性年龄相关性黄斑变性(nAMD)、息肉样脉络膜血管病变(PCV)和慢性中心性浆液性脉络膜视网膜病变(cCSCR)中的作用。病例-对照遗传关联研究。参与者共846例患者(341例nAMD, 288例PCV, 217例cCSCR,包括43例继发性黄斑新生血管[MNV])和632名健康的中国对照。方法从CFH-CFHR5区初步筛选出17个候选snp;在排除5个偏离Hardy-Weinberg平衡的snp后,保留12个snp用于最终分析。关联分析包括调整年龄和性别的逻辑回归,以及使用Haploview进行基于单倍型的分析。等位基因检测(bonferroni校正了12个snp)的全研究显著性阈值为P <; 0.0042,单倍型检测(使用10000个排列进行校正)的显著性阈值为P <; 0.05。CFH-CFHR5位点的单个snp和单倍型分别与nAMD、PCV和cCSCR(有或没有MNV)相关。结果CFHR3/1缺失的标记SNP rs12144939与nAMD显著相关(优势比[OR] = 0.37, P = 0.0031)。值得注意的是,我们发现了3个与PCV相关的候选变异,包括rs12144939 (OR = 0.29, P = 6.29 × 10-4), CFHR1中的rs423641 (OR = 0.74, P = 0.0038)和CFHR5中的rs10922152 (OR = 1.55, P = 0.0031)。该位点的SNP与cCSCR无MNV相关,而CFH rs529825与cCSCR有MNV相关(OR = 0.47, P = 0.0047)。在3种黄斑病变中观察到相似的单倍型关联模式。值得注意的是,跨越CFHR4、CFHR2和CFHR5的A-T-C-G单倍型(OR = 1.81,排列P = 0.0099)和CFHR5内的G-A-G单倍型(OR = 1.56,排列P = 0.025)与PCV特异性相关。结论本研究证实了CFHR3/1缺失(rs12144939标记)与nAMD的关联。此外,我们在CFH-CFHR5位点揭示了PCV的一个新的遗传结构,其特征是rs12144939、rs423641 (CFHR1)和rs10922152 (CFHR5)的关联,以及PCV特有的风险单倍型。这些发现强调了cfh相关基因在PCV中的关键作用,并为其遗传机制提供了新的见解。作者在本文中讨论的任何材料中没有任何专有或商业利益。
{"title":"The CFH–CFHR5 Locus in Wet Age-Related Macular Degeneration, Polypoidal Choroidal Vasculopathy, and Central Serous Chorioretinopathy","authors":"Zhen Ji Chen PhD ,&nbsp;Jun Yu MMed ,&nbsp;Mary Ho MSc ,&nbsp;Danny S.C. Ng MPH ,&nbsp;Marten E. Brelen PhD ,&nbsp;Alvin L. Young MMedSc ,&nbsp;Jason C.S. Yam MD ,&nbsp;Clement C. Tham BM, BCh ,&nbsp;Chi Pui Pang DPhil ,&nbsp;Li Jia Chen PhD","doi":"10.1016/j.xops.2025.101043","DOIUrl":"10.1016/j.xops.2025.101043","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To evaluate the effects of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement factor H–complement factor H related 5 (&lt;em&gt;CFH&lt;/em&gt;–&lt;em&gt;CFHR5&lt;/em&gt;) locus on neovascular age-related macular degeneration (nAMD), polypoidal choroidal vasculopathy (PCV), and chronic central serous chorioretinopathy (cCSCR) in Chinese patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Case-control genetic association study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants&lt;/h3&gt;&lt;div&gt;A total of 846 patients (341 nAMD, 288 PCV, and 217 cCSCR including 43 with secondary macular neovascularization [MNV]) and 632 healthy Chinese controls.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A total of 17 candidate SNPs were initially selected from the &lt;em&gt;CFH–CFHR5&lt;/em&gt; region; after excluding 5 SNPs that deviated from Hardy–Weinberg equilibrium, 12 SNPs were retained for the final analysis. Association analyses included logistic regression adjusted for age and sex and haplotype-based analysis using Haploview. Study-wide significance threshold was set at &lt;em&gt;P&lt;/em&gt; &lt; 0.0042 for allelic tests (Bonferroni-corrected for 12 SNPs) and at &lt;em&gt;P&lt;/em&gt; &lt; 0.05 for haplotype tests (adjusted using 10 000 permutations).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Associations between individual SNPs and haplotypes in the &lt;em&gt;CFH&lt;/em&gt;–&lt;em&gt;CFHR5&lt;/em&gt; locus with nAMD, PCV, and cCSCR (with or without MNV), respectively.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The tagging SNP, rs12144939, for the &lt;em&gt;CFHR3/1&lt;/em&gt; deletion was significantly associated with nAMD (odds ratio [OR] = 0.37, &lt;em&gt;P&lt;/em&gt; = 0.0031). Notably, we identified 3 candidate variants showing novel associations with PCV, including rs12144939 (OR = 0.29, &lt;em&gt;P&lt;/em&gt; = 6.29 × 10&lt;sup&gt;–4&lt;/sup&gt;), rs423641 in &lt;em&gt;CFHR1&lt;/em&gt; (OR = 0.74, &lt;em&gt;P&lt;/em&gt; = 0.0038), and rs10922152 in &lt;em&gt;CFHR5&lt;/em&gt; (OR = 1.55, &lt;em&gt;P&lt;/em&gt; = 0.0031). No SNP in this locus was associated with cCSCR without MNV, whereas &lt;em&gt;CFH&lt;/em&gt; rs529825 was nominally associated with cCSCR with MNV (OR = 0.47, &lt;em&gt;P&lt;/em&gt; = 0.0047). Similar patterns of haplotype associations were observed across the 3 maculopathies. Notably, the haplotype A-T-C-G spanning &lt;em&gt;CFHR4&lt;/em&gt;, &lt;em&gt;CFHR2,&lt;/em&gt; and &lt;em&gt;CFHR5&lt;/em&gt; (OR = 1.81, permutation &lt;em&gt;P&lt;/em&gt; = 0.0099) and haplotype G-A-G within &lt;em&gt;CFHR5&lt;/em&gt; (OR = 1.56, permutation &lt;em&gt;P&lt;/em&gt; = 0.025) were specifically associated with PCV.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This study validates the association of the &lt;em&gt;CFHR3/1&lt;/em&gt; deletion (tagged by rs12144939) with nAMD. Furthermore, we reveal a novel genetic architecture for PCV within the &lt;em&gt;CFH&lt;/em&gt;–&lt;em&gt;CFHR5&lt;/em&gt; locus, characterized by associations at rs12144939, rs423641 (&lt;em&gt;CFHR1&lt;/em&gt;), and rs10922152 (&lt;em&gt;CFHR5&lt;/em&gt;), as well as risk haplotypes unique to PCV. These findings underscore the critical role of &lt;em&gt;CFH&lt;/em&gt;-related genes in PCV and provide new insights into its genetic mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Financial Disclosures&lt;/h3&gt;&lt;div&gt;The author h","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101043"},"PeriodicalIF":4.6,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Associations between Ocular Surface Microbiome and Refractive Status in Children and Adolescents 儿童和青少年眼表微生物群与屈光状态的关系
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-12-24 DOI: 10.1016/j.xops.2025.101042
Xiangtian Ling PhD , Yu Peng MMed , Yuzhou Zhang PhD , Charlene C. Yim FCOphthHK, FRCOphth , Hei-Nga Chan PhD , Yating Yang MMed , Qihang Sun MMed , Xiu-Juan Zhang PhD , Ka Wai Kam FCOphthHK, MSc , Wai Kit Chu DPhil , Patrick Ip MD , Alvin L. Young FRCSI, MMedSc , Christopher J. Hammond MD, FRCOphth , Stephen Kwok Wing Tsui PhD , Clement C. Tham FCOphthHK, FRCOphth , Chi Pui Pang DPhil , Li Jia Chen PhD, FCOphthHK , Jason C. Yam MD, FCOphthHK

Purpose

To identify the compositional and functional alterations in the ocular surface microbiome (OSM) which are associated with myopia in children and adolescents.

Design

A population-based, cross-sectional study.

Participants

Eight hundred forty-seven children and adolescents aged 3 to 17 years were included.

Methods

Conjunctival swab samples were collected from the participants and processed via 16S ribosomal RNA gene sequencing.

Main Outcome Measures

Microbial profiles of participants were processed with QIIME2. Alpha (species diversity) and beta diversity (community structure) metrics were calculated. Microbial functional profile was predicted using PICRUSt2.

Results

Shannon (P < 0.001) and observed (P = 0.010) indexes were different among samples from myopic eyes (n = 432), as compared with those from emmetropic (n = 214) and hyperopic (n = 201) eyes. They were correlated with spherical equivalent (Shannon P = 0.0036, observed P = 0.0129) and axial length (Shannon P = 0.0057, observed P = 0.012). Beta diversity with distinct microbial signatures was unique (P < 0.05) among the eyes with myopia (Haemophilus, Aquabacterium, Anaerococcus), emmetropia (Sphingobium, Clostridium sensu stricto 1, and Fusobacterium) and hyperopia (Streptococcus, Kocuria, and Gemella). Functional profiling found enrichment of several Kyoto Encyclopedia of Genes and Genomes pathways, including oxidative phosphorylation, in the myopic ocular surface, suggesting a distinct energy utilization pattern in the myopic microbiome.

Conclusions

This study reveals distinct compositional and functional profiles in the OSM of myopic children and adolescents. These findings demonstrate an association between refractive status and the OSM; however, causality has not been established, highlighting the need for further research.

Financial Disclosures

The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.
目的探讨儿童和青少年眼表微生物组(OSM)的组成和功能变化与近视的关系。设计一项基于人群的横断面研究。参与者包括847名3至17岁的儿童和青少年。方法采集受试者结膜拭子标本,进行16S核糖体RNA基因测序。主要结局指标采用QIIME2对参与者的微生物谱进行处理。计算α(物种多样性)和β(群落结构)指标。利用PICRUSt2预测微生物功能谱。结果近视眼(n = 432)与远视眼(n = 214)和远视眼(n = 201)相比,shannon指数(P < 0.001)和observed指数(P = 0.010)存在差异。它们与球形当量(Shannon P = 0.0036,观察P = 0.0129)和轴向长度(Shannon P = 0.0057,观察P = 0.012)相关。具有不同微生物特征的β多样性在近视(血友菌、水杆菌、厌氧球菌)、斜视(鞘菌、严格感梭菌和梭菌)和远视(链球菌、Kocuria和Gemella)的眼睛中是独特的(P < 0.05)。功能分析发现,包括氧化磷酸化在内的几种京都基因和基因组百科全书通路在近视眼表面富集,这表明近视微生物组具有独特的能量利用模式。结论本研究揭示了近视儿童和青少年OSM的不同组成和功能特征。这些发现证明了折射状态与OSM之间的关联;然而,因果关系尚未确定,这突出了进一步研究的必要性。作者在本文中讨论的任何材料中没有任何专有或商业利益。
{"title":"Associations between Ocular Surface Microbiome and Refractive Status in Children and Adolescents","authors":"Xiangtian Ling PhD ,&nbsp;Yu Peng MMed ,&nbsp;Yuzhou Zhang PhD ,&nbsp;Charlene C. Yim FCOphthHK, FRCOphth ,&nbsp;Hei-Nga Chan PhD ,&nbsp;Yating Yang MMed ,&nbsp;Qihang Sun MMed ,&nbsp;Xiu-Juan Zhang PhD ,&nbsp;Ka Wai Kam FCOphthHK, MSc ,&nbsp;Wai Kit Chu DPhil ,&nbsp;Patrick Ip MD ,&nbsp;Alvin L. Young FRCSI, MMedSc ,&nbsp;Christopher J. Hammond MD, FRCOphth ,&nbsp;Stephen Kwok Wing Tsui PhD ,&nbsp;Clement C. Tham FCOphthHK, FRCOphth ,&nbsp;Chi Pui Pang DPhil ,&nbsp;Li Jia Chen PhD, FCOphthHK ,&nbsp;Jason C. Yam MD, FCOphthHK","doi":"10.1016/j.xops.2025.101042","DOIUrl":"10.1016/j.xops.2025.101042","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify the compositional and functional alterations in the ocular surface microbiome (OSM) which are associated with myopia in children and adolescents.</div></div><div><h3>Design</h3><div>A population-based, cross-sectional study.</div></div><div><h3>Participants</h3><div>Eight hundred forty-seven children and adolescents aged 3 to 17 years were included.</div></div><div><h3>Methods</h3><div>Conjunctival swab samples were collected from the participants and processed via 16S ribosomal RNA gene sequencing.</div></div><div><h3>Main Outcome Measures</h3><div>Microbial profiles of participants were processed with QIIME2. Alpha (species diversity) and beta diversity (community structure) metrics were calculated. Microbial functional profile was predicted using PICRUSt2.</div></div><div><h3>Results</h3><div>Shannon (<em>P</em> &lt; 0.001) and observed (<em>P</em> = 0.010) indexes were different among samples from myopic eyes (n = 432), as compared with those from emmetropic (n = 214) and hyperopic (n = 201) eyes. They were correlated with spherical equivalent (Shannon <em>P</em> = 0.0036, observed <em>P</em> = 0.0129) and axial length (Shannon <em>P</em> = 0.0057, observed <em>P</em> = 0.012). Beta diversity with distinct microbial signatures was unique (<em>P</em> &lt; 0.05) among the eyes with myopia (<em>Haemophilus</em>, <em>Aquabacterium</em>, <em>Anaerococcus</em>), emmetropia (<em>Sphingobium</em>, <em>Clostridium sensu stricto 1</em>, and <em>Fusobacterium</em>) and hyperopia (<em>Streptococcus</em>, <em>Kocuria</em>, and <em>Gemella</em>). Functional profiling found enrichment of several Kyoto Encyclopedia of Genes and Genomes pathways, including oxidative phosphorylation, in the myopic ocular surface, suggesting a distinct energy utilization pattern in the myopic microbiome.</div></div><div><h3>Conclusions</h3><div>This study reveals distinct compositional and functional profiles in the OSM of myopic children and adolescents. These findings demonstrate an association between refractive status and the OSM; however, causality has not been established, highlighting the need for further research.</div></div><div><h3>Financial Disclosures</h3><div>The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 3","pages":"Article 101042"},"PeriodicalIF":4.6,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Convolutional Graph Isomorphism Network to Detect Glaucomatous Visual Field Defects 卷积图同构网络检测青光眼视野缺陷
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-12-18 DOI: 10.1016/j.xops.2025.101041
Douglas R. da Costa MD , Dániel Unyi , Rafael Scherer MD, PhD , Rohit Muralidhar , Mario Luiz Ribeiro Monteiro MD, PhD , Felipe A. Medeiros MD, PhD

Purpose

To evaluate the performance of a deep learning (DL) model based on graph isomorphism networks (GINs) for detecting glaucomatous visual field defects on 24-2 standard automated perimetry (SAP) and to compare it against traditional diagnostic criteria, a dense neural network (NN) model, and a convolutional neural network (CNN) model.

Design

A cross-sectional retrospective study. Participants: 1874 reliable SAP tests (Humphrey Field Analyzer, Carl-Zeiss Meditec Inc.) from 1009 eyes of 676 patients.

Methods

Standard automated perimetry tests were classified as normal or abnormal due to glaucomatous damage by two glaucoma specialists, with adjudication by a third. A GIN architecture was developed to classify tests using full 54-point spatial SAP data modeled as graphs, with node features comprising sensitivity, total deviation, and pattern deviation values. The dataset was split at the patient level (60% training/validation, 40% testing). The GIN model’s diagnostic performance was compared to the Anderson criteria, the glaucoma hemifield test/pattern standard deviation (GHT/PSD) criteria, a fully connected dense NN, and a CNN model.

Main Outcome Measures

Area under the receiver operating characteristic curve (AUC), precision–recall curve, sensitivity at 95% specificity, F1-score, repeatability, and model explainability.

Results

Among the 1874 SAP tests, 70.0% were graded as abnormal. The GIN model achieved an AUC of 0.982, significantly outperforming the Anderson criteria (AUC: 0.906, P < 0.001), GHT/PSD (AUC: 0.936, P = 0.006), the NN model (AUC: 0.941, P = 0.007), and the CNN model (AUC: 0.941, P = 0.027). At 95% specificity, the GIN model reached the highest sensitivity of 94.1%, surpassing the NN model (88.3%), CNN model (92.0%), GHT/PSD (90.1%), and Anderson criteria (85.1%). The GIN model also achieved the highest average precision (0.952) among evaluated criteria. Explainability analysis using GraphNOSE demonstrated that the GIN model emphasized clinically relevant regions associated with glaucomatous loss, offering interpretability advantages over conventional DL approaches.

Conclusions

By modeling SAP as a graph and incorporating spatial relationships among test points, the GIN model provided superior diagnostic performance and interpretability relative to traditional criteria and standard NNs. This graph-based approach offers a promising tool for accurate and explainable detection of glaucomatous visual field defects in clinical practice.

Financial Disclosures

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
目的评价基于图同态网络(GINs)的深度学习(DL)模型在24-2标准自动视野测量(SAP)上检测青光眼视野缺陷的性能,并将其与传统诊断标准、密集神经网络(NN)模型和卷积神经网络(CNN)模型进行比较。设计横断面回顾性研究。参与者:1874个可靠的SAP测试(Humphrey Field Analyzer, Carl-Zeiss Meditec Inc.),来自676名患者的1009只眼睛。方法由两名青光眼专家将标准的自动视距检查分为青光眼损伤的正常或异常,并由第三名青光眼专家判定。开发了一个GIN架构,使用完整的54点空间SAP数据建模为图来对测试进行分类,节点特征包括灵敏度、总偏差和模式偏差值。数据集在患者层面被分割(60%用于训练/验证,40%用于测试)。将GIN模型的诊断性能与Anderson标准、青光眼半场测试/模式标准差(GHT/PSD)标准、全连接密集神经网络和CNN模型进行比较。主要结果测量:受试者工作特征曲线(AUC)下的面积、精密度-召回率曲线、95%特异性的灵敏度、f1评分、可重复性和模型可解释性。结果1874例SAP试验中,70.0%为异常。GIN模型的AUC为0.982,显著优于Anderson标准(AUC: 0.906, P < 0.001)、GHT/PSD (AUC: 0.936, P = 0.006)、NN模型(AUC: 0.941, P = 0.007)和CNN模型(AUC: 0.941, P = 0.027)。在95%的特异性下,GIN模型达到了94.1%的最高灵敏度,超过了NN模型(88.3%)、CNN模型(92.0%)、GHT/PSD(90.1%)和Anderson标准(85.1%)。GIN模型在评价标准中平均精度最高(0.952)。使用GraphNOSE进行的可解释性分析表明,GIN模型强调与青光眼丧失相关的临床相关区域,与传统DL方法相比具有可解释性优势。通过将SAP建模为图形,并结合测试点之间的空间关系,GIN模型相对于传统标准和标准神经网络具有更好的诊断性能和可解释性。这种基于图的方法为临床实践中青光眼视野缺陷的准确和可解释的检测提供了一种有前途的工具。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。
{"title":"Convolutional Graph Isomorphism Network to Detect Glaucomatous Visual Field Defects","authors":"Douglas R. da Costa MD ,&nbsp;Dániel Unyi ,&nbsp;Rafael Scherer MD, PhD ,&nbsp;Rohit Muralidhar ,&nbsp;Mario Luiz Ribeiro Monteiro MD, PhD ,&nbsp;Felipe A. Medeiros MD, PhD","doi":"10.1016/j.xops.2025.101041","DOIUrl":"10.1016/j.xops.2025.101041","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the performance of a deep learning (DL) model based on graph isomorphism networks (GINs) for detecting glaucomatous visual field defects on 24-2 standard automated perimetry (SAP) and to compare it against traditional diagnostic criteria, a dense neural network (NN) model, and a convolutional neural network (CNN) model.</div></div><div><h3>Design</h3><div>A cross-sectional retrospective study. Participants: 1874 reliable SAP tests (Humphrey Field Analyzer, Carl-Zeiss Meditec Inc.) from 1009 eyes of 676 patients.</div></div><div><h3>Methods</h3><div>Standard automated perimetry tests were classified as normal or abnormal due to glaucomatous damage by two glaucoma specialists, with adjudication by a third. A GIN architecture was developed to classify tests using full 54-point spatial SAP data modeled as graphs, with node features comprising sensitivity, total deviation, and pattern deviation values. The dataset was split at the patient level (60% training/validation, 40% testing). The GIN model’s diagnostic performance was compared to the Anderson criteria, the glaucoma hemifield test/pattern standard deviation (GHT/PSD) criteria, a fully connected dense NN, and a CNN model.</div></div><div><h3>Main Outcome Measures</h3><div>Area under the receiver operating characteristic curve (AUC), precision–recall curve, sensitivity at 95% specificity, F1-score, repeatability, and model explainability.</div></div><div><h3>Results</h3><div>Among the 1874 SAP tests, 70.0% were graded as abnormal. The GIN model achieved an AUC of 0.982, significantly outperforming the Anderson criteria (AUC: 0.906, <em>P</em> &lt; 0.001), GHT/PSD (AUC: 0.936, <em>P</em> = 0.006), the NN model (AUC: 0.941, <em>P</em> = 0.007), and the CNN model (AUC: 0.941, <em>P</em> = 0.027). At 95% specificity, the GIN model reached the highest sensitivity of 94.1%, surpassing the NN model (88.3%), CNN model (92.0%), GHT/PSD (90.1%), and Anderson criteria (85.1%). The GIN model also achieved the highest average precision (0.952) among evaluated criteria. Explainability analysis using GraphNOSE demonstrated that the GIN model emphasized clinically relevant regions associated with glaucomatous loss, offering interpretability advantages over conventional DL approaches.</div></div><div><h3>Conclusions</h3><div>By modeling SAP as a graph and incorporating spatial relationships among test points, the GIN model provided superior diagnostic performance and interpretability relative to traditional criteria and standard NNs. This graph-based approach offers a promising tool for accurate and explainable detection of glaucomatous visual field defects in clinical practice.</div></div><div><h3>Financial Disclosures</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 3","pages":"Article 101041"},"PeriodicalIF":4.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Myopia Control Interventions on Choroidal Thickness in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials 近视控制干预对儿童脉络膜厚度的影响:随机对照试验的系统回顾和荟萃分析
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-12-17 DOI: 10.1016/j.xops.2025.101039
Clara Martinez-Perez PhD , Ana Paula Oliveira PhD

Topic

This systematic review and meta-analysis evaluated whether myopia control interventions produce measurable changes in choroidal thickness (ChT) in children and adolescents with myopia compared with single-vision lenses or placebo. The primary aim was to describe patterns of ChT modulation.

Clinical Relevance

Myopia is the most common ocular disorder worldwide and is projected to affect 50% of the global population by 2050. High myopia increases the risk of complications such as myopic maculopathy and retinal detachment. Early biomarkers of treatment efficacy are critical, and ChT has emerged as a promising candidate given its rapid and bidirectional response to visual and pharmacological stimuli.

Methods

The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251144689). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) standards, randomized controlled trials (RCTs) were included if they assessed ChT changes after myopia control interventions in pediatric populations. Searches of PubMed, Web of Science, and Scopus were completed on August 5, 2025. Two reviewers independently screened, extracted, and assessed risk of bias using the Cochrane tool. Pooled mean differences with 95% confidence intervals (CIs) were calculated, and certainty of evidence was rated with Grading of Recommendations, Assessment, Development and Evaluation.

Results

Eleven RCTs including 2190 eyes were analyzed. Repeated low-level red-light therapy induced the largest thickening (mean difference = 24.1 μm, 95% CI: 19.8–28.5; I2 = 77%). Atropine produced modest but significant effects (mean difference = 10.6 μm, 95% CI: 6.7–14.5) with high heterogeneity (I2 = 97%). Orthokeratology yielded consistent increases (mean difference = 13.3 μm, 95% CI: 9.5–17.1; I2 = 6%), while lenslet spectacles showed moderate effects (mean difference = 13.2 μm, 95% CI: 5.7–20.7; I2 = 0%). Evidence certainty was rated high for most interventions and moderate for atropine.

Conclusions

Myopia control interventions produce early, measurable increases in ChT. These findings characterize patterns of choroidal modulation, while their clinical relevance remains uncertain. Further studies integrating ChT with efficacy measures are needed.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
本系统综述和荟萃分析评估了与单眼镜片或安慰剂相比,近视控制干预是否会对儿童和青少年近视患者的脉络膜厚度(ChT)产生可测量的变化。主要目的是描述ChT调制的模式。近视是世界上最常见的眼部疾病,预计到2050年将影响全球50%的人口。高度近视增加了诸如近视黄斑病变和视网膜脱离等并发症的风险。治疗效果的早期生物标志物是至关重要的,由于其对视觉和药物刺激的快速和双向反应,ChT已成为一个有希望的候选者。方法该方案已在国际前瞻性系统评价注册(PROSPERO; CRD420251144689)中注册。根据系统评价和荟萃分析的首选报告项目(PRISMA) 2020指南和评估系统评价的测量工具2 (AMSTAR-2)标准,纳入随机对照试验(rct),如果他们评估儿科人群近视控制干预后的ChT变化。PubMed、Web of Science和Scopus的检索于2025年8月5日完成。两位审稿人使用Cochrane工具独立筛选、提取和评估偏倚风险。计算95%置信区间(ci)的合并平均差异,并通过推荐、评估、发展和评价分级对证据的确定性进行评级。结果共分析了11项随机对照试验,共2190只眼。重复低强度红光治疗导致最大的增厚(平均差值为24.1 μm, 95% CI: 19.8 ~ 28.5; I2 = 77%)。阿托品产生了适度但显著的影响(平均差异= 10.6 μm, 95% CI: 6.7-14.5),异质性高(I2 = 97%)。角膜塑形镜效果一致(平均差值= 13.3 μm, 95% CI: 9.5-17.1; I2 = 6%),而透镜状眼镜效果中等(平均差值= 13.2 μm, 95% CI: 5.7-20.7; I2 = 0%)。大多数干预措施的证据确定性评级为高,阿托品的证据确定性评级为中等。结论近视控制干预措施可使视黄素含量早期明显升高。这些发现表征脉络膜调节的模式,但其临床相关性仍不确定。需要进一步研究将ChT与疗效测量相结合。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。
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引用次数: 0
ReticularNet: Automated Pixel-Level Segmentation of Reticular Pseudodrusen on Near-Infrared Reflectance Images by Deep Learning ReticularNet:基于深度学习的近红外反射图像的网状伪球像素级自动分割
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-12-17 DOI: 10.1016/j.xops.2025.101038
Souvick Mukherjee PhD , Dylan Wu , Leon von der Emde MD , Emily Vance MPH , Marco Ji MD , Mehdi Emamverdi MD , Tharindu De Silva PhD , Alisa T. Thavikulwat MD , Jayashree Kalpathy-Cramer PhD , Amitha Domalpally MD, PhD , Catherine A. Cukras MD, PhD , Tiarnán D.L. Keenan BM BCh, PhD

Objective

Reticular pseudodrusen (RPD) represent an important biomarker in age-related macular degeneration (AMD) but are difficult to grade and often assessed only for presence or absence, without quantitative or spatial analysis of RPD burden. The objective was to develop and validate a deep learning model for pixel-level RPD grading on near-infrared reflectance (NIR) images, which are commonly acquired in clinical practice and the most accurate en face detection modality.

Design

Deep learning model development study.

Participants

Five hundred eight images of 117 eyes (70 participants) with or without RPD, over a wide range of AMD severities.

Methods

The ground truth grading pipeline comprised reading center multimodal grading for RPD presence and NIR annotation with RPD contours, followed by pixel-level NIR annotation of all individual RPD lesions. The data set was split 80:20 into training and test sets. A DeepLabv3-ResNet-18 segmentation deep learning model (“ReticularNet”) was trained to perform pixel-level grading of RPD on NIR images. Its performance was compared with that of 4 ophthalmologists.

Main Outcome Measures

Dice similarity coefficient (DSC); intraclass correlation coefficient (ICC) for RPD lesion number, pixel area, and contour area.

Results

For pixel-level grading, ReticularNet achieved a mean DSC of 0.36 (standard deviation 0.16). This was significantly higher than the mean DSC of each ophthalmologist (0.03, 0.13, 0.19, and 0.23; P ≤ 0.02 for each) and of all ophthalmologists together (P < 0.0001). ReticularNet had ICCs of 0.44 (lesion number), 0.56 (pixel area), and 0.61 (contour area), with no significant underestimation or overestimation (P ≥ 0.24). These values were numerically higher than the ICCs of each ophthalmologist, who had ICC ranges of –0.08 to 0.23, –0.05 to 0.40, and –0.09 to 0.58, respectively, and significant underestimation in almost all cases. For all 3 parameters, ReticularNet’s ICC was significantly higher than that of all specialists considered together (P ≤ 0.02).

Conclusions

ReticularNet achieved automated pixel-level grading of RPD on NIR images. Its grading was superior to that of 4 ophthalmologists, across a variety of metrics. We are making the code/models available for research use. Improved access to quantitative and spatial RPD grading should lead to improved understanding of these lesions as important biomarkers of retinal disease.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
摘要:视网膜假性黄斑变性(RPD)是年龄相关性黄斑变性(AMD)的重要生物标志物,但难以分级,通常仅评估其存在与否,而没有对RPD负担进行定量或空间分析。目的是开发和验证一种深度学习模型,用于近红外反射(NIR)图像的像素级RPD分级,近红外反射(NIR)图像通常在临床实践中获得,也是最准确的人脸检测方式。设计深度学习模型开发研究。参与者:有或没有RPD的117只眼睛(70名参与者)的558张图像,超过了AMD严重程度的范围。方法ground truth分级管道包括RPD存在程度的阅读中心多模态分级和RPD轮廓的近红外注释,然后对所有个体RPD病变进行像素级近红外注释。数据集以80:20的比例分成训练集和测试集。训练DeepLabv3-ResNet-18分割深度学习模型(“ReticularNet”)对近红外图像进行像素级RPD分级。并与4名眼科医生进行比较。主要观察指标:相似系数(DSC);类内相关系数(ICC)用于RPD病灶数量、像素面积和轮廓面积。结果对于像素级分级,ReticularNet的平均DSC为0.36(标准差为0.16)。这显著高于每位眼科医生的平均DSC(0.03、0.13、0.19和0.23;P均≤0.02)和所有眼科医生的平均DSC (P < 0.0001)。ReticularNet的ICCs分别为0.44(病变数)、0.56(像素面积)和0.61(轮廓面积),无明显的低估和高估(P≥0.24)。这些数值高于每位眼科医生的ICC值,他们的ICC值范围分别为-0.08至0.23,-0.05至0.40,-0.09至0.58,几乎所有病例的ICC值都被显著低估。对于所有3个参数,ReticularNet的ICC显著高于所有专家(P≤0.02)。结论reticularnet在近红外图像上实现了RPD的像素级自动分级。在各种指标上,其评分优于4位眼科医生的评分。我们正在使代码/模型可用于研究。对定量和空间RPD分级的改进将有助于提高对这些病变作为视网膜疾病重要生物标志物的理解。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。
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引用次数: 0
Chronic Kidney Disease as a Risk Factor for Age-Related Macular Degeneration: A Prospective Cohort and Mendelian Randomization Analyses 慢性肾脏疾病是年龄相关性黄斑变性的危险因素:前瞻性队列和孟德尔随机化分析
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-12-13 DOI: 10.1016/j.xops.2025.101036
Yu Jer Hsiao , Hengtong Li MSc , Can Can Xue PhD , Crystal Chun Yuen Chong , Enwen Zhu PhD , Qiang Yuan , Marco Yu PhD , Chui Ming Gemmy Cheung MD , Qiao Fan PhD , Charumathi Sabanayagam PhD , Yih-Chung Tham PhD , Ching-Yu Cheng MD, PhD

Purpose

To evaluate shared genetic influences and investigate the association of chronic kidney disease (CKD) with the risk for advanced age-related macular degeneration (AMD).

Design

Prospective cohort study and 2-sample Mendelian randomization (MR) analyses.

Participants

Data from 430 016 participants in the UK Biobank cohort and summary statistics from the largest publicly available genome-wide association studies on estimated glomerular filtration rate (eGFR) (n = 1 004 040) and advanced AMD (n = 33 976; 16 144 cases) were analyzed.

Methods

Cox regression models were used to assess the association between CKD and incident AMD, adjusting for demographic, lifestyle, and clinical covariates. For MR analyses, we used the random-effects inverse-variance weighted model as the primary model, supported by 5 additional MR models for sensitivity analyses. A causal relationship was considered significant if P < 0.05 in the primary model and in ≥2 sensitivity models, with all MR models showing a consistent effect direction. Colocalization analysis was performed to further identify shared genetic loci linking CKD and AMD.

Main Outcome Measures

Causal associations between eGFR and advanced AMD.

Results

In the UK Biobank, baseline CKD was significantly associated with an increased risk of incident AMD (hazard ratio, 1.12; 95% confidence interval [CI], 1.01–1.25; P = 0.035) over a 10-year follow-up. Mendelian randomization analyses also demonstrated causality between lower eGFR and higher risk of advanced AMD (odds ratio, 2.03; 95% CI, 1.01–4.08; P = 0.048). Colocalization analysis indicated that the apolipoprotein E gene may contribute to this causality (rs56131196; colocalization posterior probability = 1.00, P = 2.29 x 10-33 for AMD; P = 2.29 x 10-13 for eGFR).

Conclusions

Both prospective cohort and MR analyses support causality between CKD and AMD, highlighting the need for AMD screening among patients with CKD.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
目的探讨慢性肾脏疾病(CKD)与晚期老年性黄斑变性(AMD)风险的共同遗传影响和相关性。设计前瞻性队列研究和两样本孟德尔随机化(MR)分析。研究人员分析了来自英国生物银行队列43016名参与者的数据,以及来自最大的公开全基因组关联研究的汇总统计数据,这些研究涉及肾小球滤过率(eGFR) (n = 1 004 040)和晚期AMD (n = 33 976; 16 144例)。方法采用scox回归模型评估CKD与AMD发生率之间的关系,调整人口统计学、生活方式和临床协变量。在MR分析中,我们使用随机效应反方差加权模型作为主要模型,并使用另外5个MR模型进行敏感性分析。在主要模型和≥2个敏感性模型中,因果关系为被认为是显著的P <; 0.05,所有MR模型都显示出一致的影响方向。进行共定位分析以进一步确定连接CKD和AMD的共享遗传位点。eGFR与晚期AMD之间的因果关系。结果在UK Biobank中,基线CKD与AMD发生风险增加显著相关(风险比1.12;95%可信区间[CI], 1.01-1.25; P = 0.035)。孟德尔随机化分析也显示eGFR较低与晚期AMD风险较高之间存在因果关系(优势比2.03;95% CI, 1.01-4.08; P = 0.048)。共定位分析表明载脂蛋白E基因可能与这种因果关系有关(rs56131196;共定位后验概率= 1.00,AMD的P = 2.29 x 10-33; eGFR的P = 2.29 x 10-13)。结论:前瞻性队列和MR分析均支持CKD和AMD之间的因果关系,强调CKD患者中AMD筛查的必要性。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。
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Ophthalmology science
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