Pub Date : 2026-01-09DOI: 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.
{"title":"Cholinergic Improvement of Low-Flow Segmental Aqueous Humor Outflow in Humans","authors":"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","doi":"10.1016/j.xops.2026.101070","DOIUrl":"10.1016/j.xops.2026.101070","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the influence of pharmacologic cholinergic stimulation on segmental aqueous humor outflow (AHO) in living human eyes of brain-dead organ donors.</div></div><div><h3>Design</h3><div>A prospective, nonrandomized, and interventional study.</div></div><div><h3>Subjects</h3><div>Brain-dead organ donors.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Main Outcome Measures</h3><div>Aqueous angiography fluorescent patterns, baseline AA signal intensity in various quadrants, and change in AA signal intensity after drug treatment or control.</div></div><div><h3>Results</h3><div>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, <em>P</em> < 0.001; superior vs. nasal, <em>P</em> = 0.012; and inferior vs nasal, <em>P</em> = 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; <em>P</em> < 0.001) and per eye (25.9 ± 22.9; <em>P</em> = 0.024) compared to the BSS control condition.</div></div><div><h3>Conclusions</h3><div>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.</div></div><div><h3>Financial Disclosure(s)</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 101070"},"PeriodicalIF":4.6,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079755","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}
<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
{"title":"Determining Genetic Cause of Posterior Staphylomas in Eyes with Pathologic Myopia by Whole Exome Sequencing","authors":"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","doi":"10.1016/j.xops.2025.101058","DOIUrl":"10.1016/j.xops.2025.101058","url":null,"abstract":"<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","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 3","pages":"Article 101058"},"PeriodicalIF":4.6,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079752","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}
Pub Date : 2025-12-29DOI: 10.1016/j.xops.2025.101040
Nianjia Wang , Xindi Liu , Liang Yao
{"title":"Re: Hiraoka et al: Quantitative Mapping of Posterior Eye Curvature in Children Using Distortion-Corrected OCT: Insights into Temporal Region Morphology","authors":"Nianjia Wang , Xindi Liu , Liang Yao","doi":"10.1016/j.xops.2025.101040","DOIUrl":"10.1016/j.xops.2025.101040","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 3","pages":"Article 101040"},"PeriodicalIF":4.6,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145969431","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}
Pub Date : 2025-12-24DOI: 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
{"title":"The CFH–CFHR5 Locus in Wet Age-Related Macular Degeneration, Polypoidal Choroidal Vasculopathy, and Central Serous Chorioretinopathy","authors":"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","doi":"10.1016/j.xops.2025.101043","DOIUrl":"10.1016/j.xops.2025.101043","url":null,"abstract":"<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","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}
Pub Date : 2025-12-24DOI: 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.
{"title":"Associations between Ocular Surface Microbiome and Refractive Status in Children and Adolescents","authors":"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","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> < 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> < 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}
Pub Date : 2025-12-18DOI: 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 , Dániel Unyi , Rafael Scherer MD, PhD , Rohit Muralidhar , Mario Luiz Ribeiro Monteiro MD, PhD , 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> < 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}
Pub Date : 2025-12-17DOI: 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.
{"title":"Impact of Myopia Control Interventions on Choroidal Thickness in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","authors":"Clara Martinez-Perez PhD , Ana Paula Oliveira PhD","doi":"10.1016/j.xops.2025.101039","DOIUrl":"10.1016/j.xops.2025.101039","url":null,"abstract":"<div><h3>Topic</h3><div>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.</div></div><div><h3>Clinical Relevance</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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; I<sup>2</sup> = 77%). Atropine produced modest but significant effects (mean difference = 10.6 μm, 95% CI: 6.7–14.5) with high heterogeneity (I<sup>2</sup> = 97%). Orthokeratology yielded consistent increases (mean difference = 13.3 μm, 95% CI: 9.5–17.1; I<sup>2</sup> = 6%), while lenslet spectacles showed moderate effects (mean difference = 13.2 μm, 95% CI: 5.7–20.7; I<sup>2</sup> = 0%). Evidence certainty was rated high for most interventions and moderate for atropine.</div></div><div><h3>Conclusions</h3><div>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.</div></div><div><h3>Financial Disclosure(s)</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 2","pages":"Article 101039"},"PeriodicalIF":4.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976575","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}
Pub Date : 2025-12-17DOI: 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.
{"title":"ReticularNet: Automated Pixel-Level Segmentation of Reticular Pseudodrusen on Near-Infrared Reflectance Images by Deep Learning","authors":"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","doi":"10.1016/j.xops.2025.101038","DOIUrl":"10.1016/j.xops.2025.101038","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Design</h3><div>Deep learning model development study.</div></div><div><h3>Participants</h3><div>Five hundred eight images of 117 eyes (70 participants) with or without RPD, over a wide range of AMD severities.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Main Outcome Measures</h3><div>Dice similarity coefficient (DSC); intraclass correlation coefficient (ICC) for RPD lesion number, pixel area, and contour area.</div></div><div><h3>Results</h3><div>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; <em>P</em> ≤ 0.02 for each) and of all ophthalmologists together (<em>P</em> < 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 (<em>P</em> ≥ 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 (<em>P</em> ≤ 0.02).</div></div><div><h3>Conclusions</h3><div>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.</div></div><div><h3>Financial Disclosure(s)</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 2","pages":"Article 101038"},"PeriodicalIF":4.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037948","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}
Pub Date : 2025-12-13DOI: 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。
{"title":"Chronic Kidney Disease as a Risk Factor for Age-Related Macular Degeneration: A Prospective Cohort and Mendelian Randomization Analyses","authors":"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","doi":"10.1016/j.xops.2025.101036","DOIUrl":"10.1016/j.xops.2025.101036","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate shared genetic influences and investigate the association of chronic kidney disease (CKD) with the risk for advanced age-related macular degeneration (AMD).</div></div><div><h3>Design</h3><div>Prospective cohort study and 2-sample Mendelian randomization (MR) analyses.</div></div><div><h3>Participants</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>P</em> < 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.</div></div><div><h3>Main Outcome Measures</h3><div>Causal associations between eGFR and advanced AMD.</div></div><div><h3>Results</h3><div>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; <em>P</em> = 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; <em>P</em> = 0.048). Colocalization analysis indicated that the apolipoprotein E gene may contribute to this causality (rs56131196; colocalization posterior probability = 1.00, <em>P</em> = 2.29 x 10<sup>-33</sup> for AMD; <em>P</em> = 2.29 x 10<sup>-13</sup> for eGFR).</div></div><div><h3>Conclusions</h3><div>Both prospective cohort and MR analyses support causality between CKD and AMD, highlighting the need for AMD screening among patients with CKD.</div></div><div><h3>Financial Disclosure(s)</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 2","pages":"Article 101036"},"PeriodicalIF":4.6,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037949","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}