Ophthalmology science最新文献

{"title":"Next-Generation Sequencing–Based Molecular Profiling of Conjunctival Squamous Cell Carcinoma and Its Potential Application for Therapy","authors":"Hakan Demirci MD , Josh N. Vo PhD , Yi-Mi Wu PhD , Victor Elner MD , Arul M. Chinnaiyan MD, PhD , Dan Robinson PhD , F. Yesim Demirci MD","doi":"10.1016/j.xops.2025.100801","DOIUrl":"10.1016/j.xops.2025.100801","url":null,"abstract":"<div><h3>Objective</h3><div>Targeted next-generation sequencing–based genomic and transcriptomic analyses of conjunctival squamous cell carcinoma (cSCC) samples using a panel of >1700 cancer-related genes.</div></div><div><h3>Design</h3><div>Prospective case series.</div></div><div><h3>Participants</h3><div>Twenty patients with invasive cSCC consecutively managed at an academic ocular oncology setting.</div></div><div><h3>Methods</h3><div>Integrative exome and transcriptome analysis of fresh-frozen tumor and matching normal samples.</div></div><div><h3>Main Outcome Measures</h3><div>Molecular characterization of invasive cSCCs (for somatic mutations, tumor mutation burden (TMB) and signatures, structural variations, viral transcripts, outlier gene expression) and its potential clinical applications.</div></div><div><h3>Results</h3><div>Of the 20 invasive cSCCs, only 2 were positive for human papillomavirus (HPV). All 18 HPV-negative tumors had genetic alterations in <em>TP53</em> and 16 also had alterations in <em>CDKN2A</em>. The 2 HPV-positive tumors showed no alterations in these cell cycle regulators but harbored mutations in <em>PIK3CA</em>. Other frequently altered genes included <em>KMT2C</em><em>/D</em> (70%), <em>FAT1/</em>3 (65%), and <em>NOTCH1/2/</em>3 (60%), which were implicated in both the HPV-negative and positive tumors. The average TMB was 58.41 mutations per megabase (Mut/Mb). The TMB was >20 Mut/Mb in 13 cases (65%, range: 49.3–160.8 Mut/Mb), of which 11 had ultraviolet (UV) mutational signature, 3 had APOBEC signature, and 2 had microsatellite instability. Most UV-driven tumors (8 of 11) also harbored <em>TERT</em> promoter mutations. The most recurrent large-scale copy number alterations were the deletions affecting chromosomes 3p, 9p, and 14q. Uncommon but potentially drug-targetable copy number gains were also detected affecting several oncogenes. The most frequent gene expression outlier was the aberrantly expressed <em>TP63</em> found in 19 tumors.</div></div><div><h3>Conclusions</h3><div>In our invasive cSCC cohort, HPV infection was not a major contributor to tumor etiopathogenesis. Our results confirmed the central role of <em>TP53</em> genetic alterations and the common presence of UV signature in the HPV-negative cSCCs. Irrespective of HPV status, other commonly observed genetic alterations included those affecting chromatin modifiers followed by Hippo or Notch pathway–related genes. Ultraviolet-driven <em>TERT</em> promoter mutations co-occurred with other driver gene alterations. The commonly observed high TMB makes immunotherapy a good treatment choice for invasive cSCC. Moreover, several cSCC-associated molecular alterations represent potentially actionable targets, while further studies are necessary to understand their roles in cSCC development and invasion.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end o","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 5","pages":"Article 100801"},"PeriodicalIF":3.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222576","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}

{"title":"Effect of Faricimab versus Aflibercept on Hyperreflective Foci in Patients with Diabetic Macular Edema from the YOSEMITE/RHINE Trials","authors":"Usha Chakravarthy FRCOphth, PhD ,&nbsp;Varun Chaudhary MD, FRCS(C) ,&nbsp;Srinivas R. Sadda MD ,&nbsp;Colin S. Tan FRCOphth, FRCSEd (Ophth) ,&nbsp;Stela Vujosevic MD, PhD ,&nbsp;Sascha Fauser MD ,&nbsp;Kara Gibson PhD ,&nbsp;Carl Glittenberg MD ,&nbsp;Nancy Holekamp MD, FASRS ,&nbsp;Ben Lanza PhD ,&nbsp;Andreas Maunz PhD ,&nbsp;Jeffrey R. Willis MD, PhD ,&nbsp;Rishi P. Singh MD","doi":"10.1016/j.xops.2025.100798","DOIUrl":"10.1016/j.xops.2025.100798","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare the effect of faricimab, a dual angiopoietin-2 (Ang-2) and VEGF-A inhibitor, with aflibercept on resolution of hyperreflective foci (HRF) in patients with diabetic macular edema (DME).</div></div><div><h3>Design</h3><div>A post hoc analysis of the randomized, double-masked, noninferiority YOSEMITE/RHINE (NCT03622580/NCT03622593) phase III trials.</div></div><div><h3>Participants</h3><div>Adults with vision loss due to center-involving DME.</div></div><div><h3>Methods</h3><div>A deep learning–based algorithm was used to automatically quantify HRF in spectral-domain OCT volume scans from YOSEMITE/RHINE. Study eyes were randomized to faricimab 6.0 mg every 8 weeks (Q8W; n = 519), faricimab 6.0 mg according to a personalized treat-and-extend (T&amp;E)–based regimen (n = 524), and aflibercept 2.0 mg Q8W (n = 502). Hyperreflective foci were defined as hyperreflective objects up to 50 μm in diameter and assessed within the 1.0-mm and 3.0-mm–diameter ETDRS rings and by location within the inner and outer retina.</div></div><div><h3>Main Outcome Measures</h3><div>Hyperreflective foci volume and count at baseline and over time through week 48 in the inner, outer, and total retina, 1-mm and 3-mm diameters; time to absence of HRF at 2 consecutive visits in the inner and outer retina, 1-mm diameter over 48 weeks.</div></div><div><h3>Results</h3><div>Adjusted mean HRF volumes at week 48 were lower for faricimab Q8W (104.1 picoliter [pL]) and faricimab T&amp;E (110.1 pL) compared with aflibercept (180.3 pL; nominal <em>P</em> &lt; 0.001 for both) in the inner retina, 1-mm diameter. In the inner retina, 3-mm diameter adjusted mean HRF volumes at week 48 were lower for faricimab Q8W (763.9 pL) and faricimab T&amp;E (777.2 pL) compared with aflibercept (1030.6 pL; nominal <em>P</em> &lt; 0.001 for both). Similar results were obtained for volumes in the outer retina and for HRF counts. In the inner retina, 1-mm diameter, the 25th percentile for time to absence of HRF count at 2 consecutive visits was achieved 8 weeks earlier with faricimab Q8W and faricimab T&amp;E versus aflibercept.</div></div><div><h3>Conclusions</h3><div>Greater HRF reductions were achieved with faricimab versus aflibercept, supporting the therapeutic potential of dual Ang-2/VEGF-A inhibition to suppress disease activity in DME.</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":"5 5","pages":"Article 100798"},"PeriodicalIF":3.2,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099523","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}

{"title":"Is the Incidence of Concomitant Esotropia with Diplopia in the United States Increasing?","authors":"Dae Hee Kim MD, PhD ,&nbsp;Scott R. Lambert MD","doi":"10.1016/j.xops.2025.100799","DOIUrl":"10.1016/j.xops.2025.100799","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the incidence of comitant esotropia (ET) with diplopia using a large insurance claim database in the United States.</div></div><div><h3>Design</h3><div>A retrospective cross-sectional study.</div></div><div><h3>Subjects</h3><div>A large health insurance database.</div></div><div><h3>Methods</h3><div>Claims for comitant ET with diplopia were extracted using a combination of ET- and diplopia-related codes. The claim ratio of ET to strabismus was calculated from 2007 to 2022. Age and sex distributions were compared between the first (2007–2014) and second (2015–2022) half periods.</div></div><div><h3>Main Outcome Measures</h3><div>Change of ratio of ET with diplopia to all strabismus claims.</div></div><div><h3>Results</h3><div>In total, 38 404 ET claims were identified among 1 516 779 strabismus claims. The mean age of the ET claims was 39.0 ± 17.4 years. A more marked female predominance in ET claims (male:female = 1:1.6) than in strabismus claims (1:1.1) was observed. The ET claim ratio linearly increased from 1.27% in 2007 to 3.49% in 2022 (adjusted <em>R</em>^<em>2</em> = 0.856, <em>P</em> &lt; 0.001). The mean age of the ET claims was lower in 2015 to 2022 than in 2007 to 2014 (38.4 vs. 40.0 years, <em>P</em> &lt; 0.001). The female predominance was more marked during 2015 to 2022 than in 2007 to 2014 (1:1.8 vs. 1:1.3, <em>P</em> &lt; 0.001). The sex distribution of the younger age group (&lt;39 years) changed from male predominance in 2007 to 2014 to female predominance in 2015 to 2022.</div></div><div><h3>Conclusions</h3><div>The proportion of comitant ET with diplopia in strabismus has increased since 2007 in the United States. The increase was most pronounced in young patients. Female predilection in comitant ET with diplopia was observed, and the change from male to female predominance over time was remarkable among young patients.</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":"5 5","pages":"Article 100799"},"PeriodicalIF":3.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089319","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}

{"title":"Developing Laterality-Specific Computable Phenotypes from Electronic Health Record Data, Employing Treatment-Warranted Diabetic Macular Edema as a Use Case","authors":"Kaili Ding MBBS, MS ,&nbsp;Tracy Z. Lang BS ,&nbsp;Roberta McKean-Cowdin PhD ,&nbsp;Hossein Ameri MD, PhD ,&nbsp;Narsing A. Rao MD ,&nbsp;Brian C. Toy MD","doi":"10.1016/j.xops.2025.100797","DOIUrl":"10.1016/j.xops.2025.100797","url":null,"abstract":"<div><h3>Purpose</h3><div>To develop a general algorithm employing structured and unstructured electronic health record (EHR) data to identify laterality-specific treatment-warranted disease more accurately at the longitudinal eye level.</div></div><div><h3>Design</h3><div>A retrospective treatment-warranted diabetic macular edema (TW-DME) cohort study.</div></div><div><h3>Subjects</h3><div>Patients with diabetic retinopathy (DR) identified from a health safety net system and a university hospital in Los Angeles, California, employing diagnosis and procedure codes from 2013 to 2023.</div></div><div><h3>Methods</h3><div>We investigated the completeness and accuracy of laterality-specific TW-DME status based on the following 5 categories of data: Tier 1-Physician Procedure Documentation, Tier 2-Charge Codes (Professional and Facility), Tier 3-Medication Orders, Tier 4-Crosswalked Procedure Codes, and Tier 5-Diagnosis Code associated with Procedure. Laterality data completeness was evaluated for each category, independently and in a tiered hierarchical order. Data accuracy was verified by manual chart review for a subset of validation patients.</div></div><div><h3>Main Outcome Measures</h3><div>Algorithm performance in ascertaining cross-sectional and longitudinal TW-DME status.</div></div><div><h3>Results</h3><div>From 2013 to 2023, 7784 patients with DR had 68 465 visits, with 4809 (61.8%) patients identified as having TW-DME. Notably, 67.9% of health safety net patients had visits with missing diagnosis laterality. The proposed algorithm improved laterality completeness in the treatment-warranted DR cohort to 93.6% for the safety net and 99.0% for the university sites. Validation by chart review demonstrated an increase in positive predictive value (safety net 47.0%–93.2%, university 85.3%–98.8%), negative predictive value (safety net 23.2%–33.3%, university 46.9%–72.6%), sensitivity (safety net 35.9%–76.0%, university 79.2%–96.0%), specificity (safety net 60.4%–76.6%, university 38.8%–90.4%), agreement (safety net 38.5%–76.1%, university 74.8%–95.4%), and F1 score (safety net 40.7%–83.7%, university 82.1%–97.4%) at the longitudinal eye level.</div></div><div><h3>Conclusions</h3><div>Our algorithm employing structured and unstructured data lays out a general and reproducible approach to more accurately identify and extract laterality-specific data from EHRs. This method was valid across sites with disparate documentation and coding practices. Application of this algorithm could improve the utility of clinical data generated as part of routine care for future investigations of ocular disease prevalence, sequelae, treatment patterns, and costs.</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":"5 5","pages":"Article 100797"},"PeriodicalIF":3.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166801","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}

{"title":"Oral Antithrombotic Medication Is Associated with Improved Visual Outcomes in Eyes with Submacular Hemorrhage from Wet Age-Related Macular Degeneration","authors":"Hemal P. Patel MD,&nbsp;Cason B. Robbins MD,&nbsp;Jamie J. Karl MD,&nbsp;Peter Weng MD, PhD,&nbsp;Lejla Vajzovic MD, FASRS,&nbsp;Sharon Fekrat MD, FASRS","doi":"10.1016/j.xops.2025.100796","DOIUrl":"10.1016/j.xops.2025.100796","url":null,"abstract":"<div><h3>Purpose</h3><div>To determine differences in visual acuity (VA) outcomes in eyes of patients on antithrombotics (antiplatelet agents and anticoagulants) that develop submacular hemorrhage (SMH) compared with eyes of patients who are not on antithrombotics and develop SMH.</div></div><div><h3>Design</h3><div>A retrospective study of patients presenting with fovea-involving SMH due to wet age-related macular degeneration over an 8-year period who had ≥6 months of follow-up.</div></div><div><h3>Subjects</h3><div>Demographics, VA at presentation and final follow-up after SMH management, and history of any antithrombotic therapy were collected. Patients were grouped based on whether they were on anticoagulants (direct oral anticoagulants or warfarin), antiplatelet agents (P2Y12 inhibitors, aspirin, or both), or neither.</div></div><div><h3>Methods</h3><div>Multivariate generalized estimating equations were used for statistical analysis.</div></div><div><h3>Main Outcome Measures</h3><div>The difference between VA at presentation with SMH and VA at final follow-up was compared between patients taking oral anticoagulants or antiplatelet agents and those not on any antithrombotic agent.</div></div><div><h3>Results</h3><div>Seventy-seven eyes of 74 patients were included. Twenty were on oral anticoagulants, 38 were on antiplatelet agents, and 22 were on neither. After controlling for age, sex, post-SMH cataract surgery, time to presentation, treatments received, initial VA, and follow-up duration, patients taking oral anticoagulants had greater improvement in VA at final follow-up compared with patients who were not taking a concurrent antithrombotic agent (<em>P</em> = 0.001); however, patients on oral antiplatelets did not (<em>P</em> = 0.09). After additionally controlling for the initial size and thickness of SMH, patients taking oral anticoagulants and patients taking oral antiplatelets had greater improvement in VA at final follow-up compared with patients who were not taking an antithrombotic (<em>P</em> = 0.002 and <em>P</em> &lt; 0.001, respectively).</div></div><div><h3>Conclusions</h3><div>Patients taking oral anticoagulants who then develop an SMH may have better long-term VA outcomes than those who were not. However, this effect was not seen in patients taking oral antiplatelet medications. This suggests that baseline anticoagulants may be associated with improved VA outcomes in eyes that develop an SMH. When controlling for size and thickness of SMH, patients taking oral anticoagulants and those taking oral antiplatelets had better long-term VA outcomes than those who were not, suggesting a potential mitigating effect of oral antithrombotics.</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":"5 5","pages":"Article 100796"},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948325","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}

{"title":"Risk of Retinal Vascular Occlusive Disease in Patients with Aortic Stenosis","authors":"Minjeong Kim MD ,&nbsp;Eui-Young Choi MD, PhD ,&nbsp;Kunho Bae MD ,&nbsp;Ju-Yeun Lee MD, PhD","doi":"10.1016/j.xops.2025.100795","DOIUrl":"10.1016/j.xops.2025.100795","url":null,"abstract":"<div><h3>Objective</h3><div>The intersection of aortic stenosis (AS) and retinal vascular occlusive disease (RVOD) underscores the need for comprehensive cardiovascular and ophthalmic evaluations in patients with either condition. We aimed to evaluate the risk of RVOD in the entire Korean population with AS.</div></div><div><h3>Design</h3><div>A population-based retrospective cohort study.</div></div><div><h3>Participants</h3><div>We included 4094 patients with AS (2088 males) and 4094 age-, sex-, and index year-matched controls. Clinical and follow-up data of all patients diagnosed with AS and healthy controls from 2004 to 2015 were extracted from the Korean National Health Insurance Claim database.</div></div><div><h3>Methods</h3><div>The risk of RVOD, including retinal vein occlusion and retinal artery occlusion, was compared between the AS and control groups. Competing analysis was used to obtain aHRs. The covariates used in the final analysis included age, sex, income, body mass index, fasting glucose, systolic blood pressure, cholesterol level, smoking, alcohol consumption, atrial fibrillation (AF), and myocardial infarction (MI).</div></div><div><h3>Main Outcome Measures</h3><div>Adjusted hazard ratio (aHR) of RVOD, incidence rate of RVOD.</div></div><div><h3>Results</h3><div>The incidence rate of RVOD per 100 000 was 495.3 in the AS group and 366.2 in the control group (<em>P</em> &lt; 0.001). During a mean follow-up period of 8 years, the aHR of RVOD was 1.48 (95% confidence interval [CI]: 1.19–1.83) in the AS group compared with the control group. Even after adjusting for AF and MI, the incidence of RVOD remained consistently and significantly higher in patients with AS (aHR 1.29, 95% CI: 1.03–1.63). In the subgroup analysis based on age, the risk of RVOD was significantly higher in patients with AS across all age groups. However, this significance weakened after adjusting for MI in patients ≥80 years (aHR 7.47, 95% CI: 0.97–57.55) and for AF in patients ≥65 years (aHR 1.36, 95% CI: 0.92–2.03).</div></div><div><h3>Conclusions</h3><div>The results suggest a possible clinical association between AS and subsequent RVOD. Continuous screening for ≥5 years for RVOD would be recommended in patients with AS.</div></div><div><h3>Financial Disclosure(s)</h3><div>The author(s) have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 5","pages":"Article 100795"},"PeriodicalIF":3.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089253","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}

{"title":"Plasma Proteomic Markers of Interleukin-1β Pathway Associated with Incident Age-Related Macular Degeneration in Persons with AIDS","authors":"Peter W. Hunt MD ,&nbsp;Adam B. Olshen PhD ,&nbsp;Natalia Murad PhD ,&nbsp;Gabrielle C. Ambayec BS ,&nbsp;Efe Sezgin PhD ,&nbsp;Michael F. Schneider MS ,&nbsp;Douglas A. Jabs MD, MBA","doi":"10.1016/j.xops.2025.100794","DOIUrl":"10.1016/j.xops.2025.100794","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the associations of plasma inflammatory proteins with age-related macular degeneration (AMD) in persons with the AIDS, using a discovery-based proteomics approach.</div></div><div><h3>Design</h3><div>A nested case-control study (analysis 1) and nested cohort study (analysis 2).</div></div><div><h3>Participants</h3><div>Persons with AIDS enrolled in the Longitudinal Study of the Ocular Complications with AIDS (LSOCA).</div></div><div><h3>Methods</h3><div>Cryopreserved plasma specimens obtained at baseline were assayed for inflammatory proteins using the Olink Inflammation Explore Panel 1. In analysis 1, baseline proteomic profiles for 26 persons with AIDS and incident intermediate-stage AMD 5 to 10 years after baseline and 49 matched controls (matched for age, biologic sex, race/ethnicity, and follow-up) without AMD were compared. In analysis 2, 475 persons from LSOCA with baseline plasma inflammatory proteomic profile measurements were followed for incident cataract and mortality.</div></div><div><h3>Main Outcome Measures</h3><div>Incident intermediate-stage AMD; incident cataract; and mortality.</div></div><div><h3>Results</h3><div>Of 365 measurable plasma inflammatory proteins, 118 (32%) were associated with incident intermediate-stage AMD at the false discovery rate-adjusted Q &lt; 0.05 level after adjustment for smoking, CD4+ T count, and plasma human immunodeficiency virus RNA level. Gene ontology pathway enrichment analysis identified the interleukin (IL)-1β pathway and wound healing pathways, including tissue inhibitor of metalloproteinase 3, as significantly associated with incident AMD. These associations were qualitatively different from those associated with incident cataracts, where elevated levels of inflammatory proteins were associated with a decreased risk of cataracts. A much broader number of inflammatory pathways, including those related to the adaptive immune system, were associated with mortality.</div></div><div><h3>Conclusions</h3><div>Upregulation of the IL-1β pathway appears to be associated with an increased risk of incident AMD in persons with AIDS. Given the availability of inhibitors of this pathway, inhibition of the IL-1β pathway may provide a therapeutic avenue for treatment of AMD.</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":"5 5","pages":"Article 100794"},"PeriodicalIF":3.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167422","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}

{"title":"Systematic Review of Proteomics in Age-Related Macular Degeneration and Pathway Analysis of Significant Protein Changes","authors":"Olympia Sideri MD, MSc ,&nbsp;Victor Correa MD ,&nbsp;Nikolaos Ziakas MD, PhD ,&nbsp;Ioannis Tsinopoulos MD, PhD ,&nbsp;Joan W. Miller MD, PhD ,&nbsp;Demetrios G. Vavvas MD, PhD","doi":"10.1016/j.xops.2025.100793","DOIUrl":"10.1016/j.xops.2025.100793","url":null,"abstract":"<div><h3>Topic</h3><div>Proteomics in age-related macular degeneration (AMD) research.</div></div><div><h3>Clinical Relevance</h3><div>AMD is the leading cause of blindness in industrialized countries, with a poorly understood pathogenesis. Proteomics can identify significantly altered proteins in AMD patients, aiding in understanding the disease’s pathophysiology and potentially improving diagnosis or treatment strategies.</div></div><div><h3>Methods</h3><div>A systematic review of proteomic studies in AMD was conducted. Proteins significantly altered in dry and wet AMD and those tested as biomarkers were presented according to sample type (aqueous humor, plasma, urine, vitreous, retinal pigment epithelium/choroid, and tear film) and type of assay (mass spectrometry or aptamers) used in the individual studies. Proteins that exhibited at least a 2× fold change (FC) were further analyzed through functional enrichment analysis and protein–protein interaction networks (STRING database).</div></div><div><h3>Results</h3><div>Twenty-two studies (case-control and cohorts) with a total of 6932 participants were included. The included studies showed significant heterogeneity, and most of them lacked sufficient power. Results suggested that various proteins and pathways are implicated in AMD, and there were differences when comparing results from the individual studies and unbiased results. Although many proteins differed significantly between AMD and control groups, most exhibited less than a 2-FC. Functional analysis of proteins with ≥|2|-FCs (identified by unbiased proteomics in multiple biofluids) highlighted lipid metabolism and protease regulation pathways as central to both dry and wet AMD. Complement and coagulation cascades, chaperones, and glycolysis pathways were significant in wet AMD, whereas matrix remodeling pathways were enriched mostly in dry AMD.</div></div><div><h3>Conclusion</h3><div>Combining proteomics from various studies could reveal new protein–protein interaction networks and associated functional pathways that may suggest novel potential therapeutic targets for AMD. However, there is a scarcity of data available for early AMD from ocular biofluids, and it should be the aim of future proteomics studies.</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":"5 5","pages":"Article 100793"},"PeriodicalIF":3.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099524","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}

{"title":"Quantification of Hyperreflective Foci in Age-related Macular Degeneration by Polarization-Sensitive OCT","authors":"Ryo Terao MD, PhD ,&nbsp;Shuichiro Aoki MD, PhD ,&nbsp;Kohdai Kitamoto MD, PhD ,&nbsp;Kota Totani AE ,&nbsp;Masahiro Yamanari PhD ,&nbsp;Satoshi Sugiyama MSc ,&nbsp;Tatsuya Inoue MD, PhD ,&nbsp;Ryo Obata MD, PhD ,&nbsp;Keiko Azuma MD, PhD","doi":"10.1016/j.xops.2025.100792","DOIUrl":"10.1016/j.xops.2025.100792","url":null,"abstract":"<div><h3>Purpose</h3><div>To quantify hyperreflective foci (HRF) using polarization-sensitive OCT (PS-OCT) and evaluate the effect of anti-VEGF therapy on HRF reduction.</div></div><div><h3>Design</h3><div>Retrospective study.</div></div><div><h3>Subjects</h3><div>Twelve eyes from 12 patients with neovascular age-related macular degeneration (nAMD) who underwent PS-OCT imaging before and after 4 intravitreal injections of faricimab, administered every 4 weeks.</div></div><div><h3>Methods</h3><div>Retinal layers between the inner border of the inner nuclear layer and the outer border of the outer segment of photoreceptors were analyzed. Regions with entropy values exceeding the mean + 2 standard deviations from healthy controls (entropy: 0.0896 ± 0.0270) were isolated to quantify hyperentropic foci (HEF), representing HRF.</div></div><div><h3>Main Outcome Measures</h3><div>The sum and area of HEF were calculated as total HEF and area aggregate to compare before and after the treatment.</div></div><div><h3>Results</h3><div>The mean patient age was 77.4 ± 8.6 years, with an equal distribution of males and females (6 each). Total HEF was significantly associated with worse baseline visual acuity (coefficient: 0.0015297, <em>P</em> = 0.0004). Faricimab treatment significantly reduced both total HEF (<em>P</em> = 0.0049) and area aggregate (<em>P</em> = 0.0068). However, conventional OCT did not detect significant improvements in total reflectivity nor area aggregate.</div></div><div><h3>Conclusions</h3><div>Polarization-sensitive OCT is a valuable imaging modality for extracting and quantifying HRF in the neurosensory retina. Faricimab significantly reduces HEF in nAMD eyes, highlighting its potential therapeutic effect beyond conventional OCT-detected changes.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosures may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 5","pages":"Article 100792"},"PeriodicalIF":3.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139462","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}

{"title":"Re: Chaurasia et al: Highly Accurate and Precise Automated Cup-to-Disc Ratio Quantification for Glaucoma Screening","authors":"Eunice Jin Hui Goh MMed (Ophth), FRCOphth ,&nbsp;Boon Peng Yap BEng ,&nbsp;Kelvin Zhenghao Li MMed (Ophth), FRCOphth","doi":"10.1016/j.xops.2025.100788","DOIUrl":"10.1016/j.xops.2025.100788","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 5","pages":"Article 100788"},"PeriodicalIF":3.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886745","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}