Ophthalmology science最新文献

{"title":"Scleral Thickness in Eyes with Pachychoroid Pigment Epitheliopathy Accompanied by Keratoconus","authors":"Paolo Forte MD ,&nbsp;Alessandro Feo MD ,&nbsp;Hideki Koizumi MD, PhD ,&nbsp;Enrico Borrelli MD, PhD ,&nbsp;Riccardo Manocchio MD ,&nbsp;Luca Di Cello MD, PhD ,&nbsp;Francesco Biagini MD ,&nbsp;Francesco Macocco MD ,&nbsp;Gabriele Drago MD ,&nbsp;Giovanni Forte MD ,&nbsp;Aldo Vagge MD, PhD ,&nbsp;Christian Gianoglio PhD ,&nbsp;Vincenzo Fontana PhD ,&nbsp;Michele Iester MD, PhD ,&nbsp;Massimo Nicolò MD, PhD ,&nbsp;Mario R. Romano MD, PhD ,&nbsp;Chiara Bonzano MD, PhD","doi":"10.1016/j.xops.2025.100808","DOIUrl":"10.1016/j.xops.2025.100808","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the prevalence of pachychoroid pigment epitheliopathy (PPE) in eyes with keratoconus (KC) and investigate its correlation with corneal, choroidal, and scleral indices with multimodal imaging.</div></div><div><h3>Design</h3><div>An exploratory, cross-sectional, cohort study.</div></div><div><h3>Subjects</h3><div>One hundred consecutive patients affected with KC.</div></div><div><h3>Main Outcome Measures</h3><div>Scleral stromal thickness, PPE prevalence, and their associations with corneal and choroidal parameters.</div></div><div><h3>Methods</h3><div>Demographic data, corneal collagen cross-linking, anamnestic records, and clinical findings were collected. Imaging protocol included OCT (Spectralis HRA+OCT; Heidelberg Engineering), corneal topography (TMS-4N, Tomey), corneal pachymetry (RTVue-XR Avanti, Optovue), and axial length (AXL) measurement (OA-2000, Tomey). Anterior scleral stromal thickness was measured in the horizontal gaze positions 6 mm posteriorly to the scleral spur (Spectralis HRA+OCT; linear 20° scan, 1024 A-scan per second). Odds ratios (ORs) and corresponding 95% confidence limits (95% CLs) were estimated through logistic regression analysis to evaluate the association between each study parameter and PPE. To accommodate for the potential clustering effect due to within-patient correlated eye data, a generalized estimating equation procedure was applied to regression analysis. Additionally, a decision tree machine learning model with K-fold cross-validation was employed to predict PPE.</div></div><div><h3>Results</h3><div>Eighty-five Caucasian patients were eligible for analysis (mean age: 34.2 years, standard deviation: 8.7). The prevalence of PPE was 10.5% (95% CL: 4.9/19.1%; 9/85 patients; 11/170 eyes; 2 bilateral cases). Significant predictors for PPE according to logistic regression were choroidal thickness (OR: 4.51; 95% CL: 1.50/13.6 for 50 μm increments; <em>P</em> = 0.007), age (OR: 4.61; 95% CL: 1.30/16.4 for 10-year increments; <em>P</em> = 0.018), and scleral stromal thickness (OR: 7.48: 95% CL: 1.69/33.1 for 25 μm increments; <em>P</em> = 0.008). Sex, AXL, corneal curvature, and astigmatism parameters did not show significant discriminant ability (<em>P</em> &gt; 0.05). Collagen cross-linking treatment was performed in a comparable proportion between the 2 groups (73.6% vs. 63.4% in PPE and non-PPE, respectively).</div></div><div><h3>Conclusions</h3><div>Our study identifies increased scleral thickness as the key predictor of PPE in KC patients, followed by choroidal thickening and increased age. These findings provide new insights into the role of scleral biomechanics in KC eyes with PPE.</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 100808"},"PeriodicalIF":3.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222434","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":"Double-Masked, Dose-Response, Vehicle-Controlled Study of VVN461 Ophthalmic Solution in Postoperative Ocular Inflammation","authors":"James H. Peace MD ,&nbsp;Kevin Y. Jong MD ,&nbsp;Jason Bacharach MD ,&nbsp;Xiao-Yan Li MD ,&nbsp;Wang Shen PhD ,&nbsp;Caroline Lu MS ,&nbsp;Gary D. Novack PhD ,&nbsp;VVN461-CS201 Study Group","doi":"10.1016/j.xops.2025.100806","DOIUrl":"10.1016/j.xops.2025.100806","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the safety and ocular efficacy of VVN461, a Janus kinase kinase inhibitor, for treatment of postoperative inflammation.</div></div><div><h3>Design</h3><div>This was a phase II, multicenter, double-masked, randomized, vehicle-controlled, parallel-comparison study in subjects who underwent routine unilateral cataract extraction and lens replacement surgery via phacoemulsification without surgical complication.</div></div><div><h3>Participants</h3><div>Ninety-one subjects at 9 private practice US ophthalmology offices.</div></div><div><h3>Intervention</h3><div>VVN61 0.5% and 1.0% topical ophthalmic solution or vehicle, 4 times daily.</div></div><div><h3>Main Outcome Measures</h3><div>The proportion of subjects with anterior chamber cell (ACC) grade 0 in the study eye at day 14.</div></div><div><h3>Results</h3><div>The proportion of subjects with ACC grade 0 in the study eye at day 14 was 60.0% (18/30), 53.3% (16/30), and 19.4% (6/31) in the VVN461, 1.0%, VVN461, 0.5%, and vehicle groups, respectively (<em>P</em> = 0.0012 and 0.0057). Treatment effects in favor of VVN461 were also seen in the need for rescue medication and reduction of anterior chamber flare. There were relatively few adverse events in either VVN461 treatment group (10%, 3/30, or less), and they were judged of mild severity.</div></div><div><h3>Conclusions</h3><div>In this double-masked, vehicle-controlled study, clinically and statistically significant anti-inflammatory efficacy was seen with few safety issues.</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 100806"},"PeriodicalIF":3.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139464","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":"Explainable Artificial Intelligence–Assisted Exploration of Clinically Significant Diabetic Retinal Neurodegeneration on OCT Images","authors":"Miyo Yoshida MD,&nbsp;Tomoaki Murakami MD, PhD,&nbsp;Kenji Ishihara MD, PhD,&nbsp;Yuki Mori MD, PhD,&nbsp;Akitaka Tsujikawa MD, PhD","doi":"10.1016/j.xops.2025.100804","DOIUrl":"10.1016/j.xops.2025.100804","url":null,"abstract":"<div><h3>Purpose</h3><div>To explore clinically significant diabetic retinal neurodegeneration in OCT images using explainable artificial intelligence (XAI) and subsequent evaluation by retinal specialists.</div></div><div><h3>Design</h3><div>A single-center, retrospective, consecutive case series.</div></div><div><h3>Participants</h3><div>Three hundred ninety-seven eyes from 397 diabetic retinopathy patients for XAI-based screening and 244 fellow eyes for subjective human evaluation.</div></div><div><h3>Methods</h3><div>We acquired 30° horizontal OCT images centered on the fovea. An artificial intelligence (AI) model was developed to infer visual acuity (VA) reduction using fine-tuned RETFound-OCT. Attention maps highlighting regions contributing to VA inference were generated using layer-wise relevance propagation. Retinal specialists assessed OCT findings based on salient regions indicated by XAI. Two newly described findings, a needle-like appearance of the ganglion cell layer (GCL)/inner plexiform layer (IPL) (“ice-pick sign”) and dot-like alterations in the outer nuclear layer (ONL) (“salt-and-pepper sign”), were evaluated alongside 2 established findings: EZ disruption and choroidal hypertransmission.</div></div><div><h3>Main Outcome Measures</h3><div>Identification of clinically significant OCT findings associated with diabetic retinal neurodegeneration.</div></div><div><h3>Results</h3><div>The AI model effectively discriminated eyes with poor vision (decimal VA ≤0.5) from those with good vision (VA ≥1.0) (area under the receiver operating characteristic curve of 0.947). Explainable artificial intelligence–based attention maps highlighted salient regions in the GCL/IPL (65.2% or 70.0%), ONL (52.2% or 28.3%), EZ (39.1% or 21.7%), and choroid (26.1% or 5.00%) in eyes with poor or good vision, respectively. Subjective evaluation by retinal specialists revealed the frequencies of these 4 findings as follows: ice-pick sign (32.4%), EZ disruption (25.0%), salt-and-pepper sign (16.0%), and choroidal hypertransmission (13.5%). Eyes with decimal VA ≤0.9 had these findings more frequently than those with VA ≥1.0 (<em>P</em> &lt; 0.001 for all comparisons). Salt-and-pepper sign and choroidal hypertransmission exhibited high specificity for identifying eyes with poor vision. Statistical analyses demonstrated more significant associations between EZ disruption, salt-and-pepper sign, and hypertransmission compared with their relationships with the ice-pick sign.</div></div><div><h3>Conclusions</h3><div>Artificial intelligence–assisted exploration of OCT findings identified 2 established lesions and 2 novel OCT biomarkers indicative of clinically significant diabetic retinal neurodegeneration.</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 100804"},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144154504","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":"Impact of Social Vulnerability Index and Distance to Tertiary Ocular Emergency Department in Patients Presenting with Open Globe Injury","authors":"Davina A. Malek MD ,&nbsp;Jason A. Greenfield BS ,&nbsp;Timothy Norris PhD ,&nbsp;Swarup S. Swaminathan MD ,&nbsp;Kara M. Cavuoto MD","doi":"10.1016/j.xops.2025.100802","DOIUrl":"10.1016/j.xops.2025.100802","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the impact of Social Vulnerability Index (SVI) and the distance to a tertiary eye emergency department (ED) on presenting visual acuity (VA), final VA, and rates of VA change over time in patients presenting with open globe injury (OGI).</div></div><div><h3>Design</h3><div>Retrospective cohort study.</div></div><div><h3>Participants</h3><div>Patients with OGI from 2018 to 2021 were identified from the electronic health records using the International Classification of Diseases coding system.</div></div><div><h3>Methods</h3><div>Data collected included demographics, insurance status, follow-up visits, and VA measurements. Social Vulnerability Index scores were calculated using a US Census Geocoder and stratified into quartiles, and distances to the eye ED were calculated. Simple logistic regression models evaluated the associations of presenting and final VAs with SVI, distance, baseline characteristics, and time from injury to presentation, adjusting for potential confounders. Univariable and multivariable linear regression models analyzed the associations between VA rates of change over time and SVI, distance to ED, demographics, insurance, and presenting VA.</div></div><div><h3>Main Outcome Measures</h3><div>The relationship between SVI and distance on presenting VA, final VA, and rates of longitudinal VA change over time.</div></div><div><h3>Results</h3><div>A total of 446 patients presented with an OGI. Of these patients, 337 (75.0%) with complete SVI data were included in the final analysis. Social Vulnerability Index was associated with nearly a fourfold increased risk of worse presenting VA in populations with higher vulnerability compared with those with lower overall vulnerability (odds ratio [OR] = 3.85; 95% confidence interval [CI]: 1.34–11.05; <em>P</em> = 0.012). Greater distance from the eye ED was also a contributing factor to higher risk of poorer presenting VA (OR = 2.55; 95% CI: 1.42–4.60; <em>P</em> = 0.002). On multivariable analyses, longitudinal VA change over time was not impacted by SVI (<em>P</em> &gt; 0.05 for all groups), and final visual outcome was not associated with either SVI or distance to the eye ED.</div></div><div><h3>Conclusions</h3><div>Greater distances from the eye ED and social vulnerability were associated with a higher risk of worse VA at presentation. However, no significant impact of SVI or distance was observed on long-term VA changes and final visual outcome on the multivariable analyses.</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 100802"},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139463","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":"A Hybrid Deep Learning–Based Approach for Visual Field Test Forecasting","authors":"Ashkan Abbasi PhD ,&nbsp;Sowjanya Gowrisankaran PhD ,&nbsp;Wei-Chun Lin MD, PhD ,&nbsp;Xubo Song PhD ,&nbsp;Bhavna Josephine Antony PhD ,&nbsp;Gadi Wollstein MD ,&nbsp;Joel S. Schuman MD ,&nbsp;Hiroshi Ishikawa MD","doi":"10.1016/j.xops.2025.100803","DOIUrl":"10.1016/j.xops.2025.100803","url":null,"abstract":"<div><h3>Objective</h3><div>Longitudinal assessment of visual field (VF) testing is essential in glaucoma management. Conventional VF forecasting methods require numerous prior tests, while deep learning techniques have shown promising results with fewer tests. This study introduces a hybrid deep learning framework to enhance flexibility and accuracy in VF test forecasting.</div></div><div><h3>Design</h3><div>A retrospective longitudinal study using deep learning–based VF forecasting models.</div></div><div><h3>Subjects and Controls</h3><div>A total of 1750 subjects (healthy and glaucoma patients) with 19 437 Humphrey VF (24-2 Swedish Interactive Threshold Algorithm) tests collected from longitudinal glaucoma cohorts at the University of Pittsburgh and New York University.</div></div><div><h3>Methods</h3><div>Three deep learning models were trained for pointwise forecasting of VF test data: (1) a recurrent neural network (RNN), (2) CascadeNet-5, a convolutional neural network (CNN), and (3) Hybrid-VF-Net, our proposed method that combines an RNN with a CNN equipped with depthwise transformers for both spatial and temporal modeling. The results were analyzed from multiple perspectives, including the impact of varying the amount of prior input data and how data reliability and disease severity influence VF forecasting performance.</div></div><div><h3>Main Outcome Measures</h3><div>Mean absolute error between predicted and actual VF test results was evaluated using five-fold cross-validation.</div></div><div><h3>Results</h3><div>We found that specific VF locations benefited more from either local or temporal modeling, and our proposed methods outperformed the compared approaches using a hybrid strategy. Hybrid-VF-Net exhibited greater resilience to data reliability issues, particularly in managing high false-negative rates often seen in moderate-to-severe glaucoma cases due to increased test–retest variability. Additionally, it demonstrated improved performance with fewer prior VF tests, thus reducing the waiting time needed for progression analysis.</div></div><div><h3>Conclusions</h3><div>The proposed Hybrid-VF-Net method outperformed the existing deep learning VF methods in terms of performance and robustness. Our findings highlight the influence of disease severity, data quality, and time displacement on forecasting performance, with certain VF locations benefiting more from either local or temporal modeling. Low reliability in data from moderate to advanced glaucoma cases continues to pose a challenge. Therefore, future research could refine temporal modeling and leverage larger datasets to further enhance predictive performance.</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 100803"},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166802","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":"Next-Generation Sequencing–Based Molecular Profiling of Conjunctival Squamous Cell Carcinoma and Its Potential Application for Therapy","authors":"Hakan Demirci MD ,&nbsp;Josh N. Vo PhD ,&nbsp;Yi-Mi Wu PhD ,&nbsp;Victor Elner MD ,&nbsp;Arul M. Chinnaiyan MD, PhD ,&nbsp;Dan Robinson PhD ,&nbsp;F. Yesim Demirci MD","doi":"10.1016/j.xops.2025.100801","DOIUrl":"10.1016/j.xops.2025.100801","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Targeted next-generation sequencing–based genomic and transcriptomic analyses of conjunctival squamous cell carcinoma (cSCC) samples using a panel of &gt;1700 cancer-related genes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Prospective case series.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants&lt;/h3&gt;&lt;div&gt;Twenty patients with invasive cSCC consecutively managed at an academic ocular oncology setting.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Integrative exome and transcriptome analysis of fresh-frozen tumor and matching normal samples.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Of the 20 invasive cSCCs, only 2 were positive for human papillomavirus (HPV). All 18 HPV-negative tumors had genetic alterations in &lt;em&gt;TP53&lt;/em&gt; and 16 also had alterations in &lt;em&gt;CDKN2A&lt;/em&gt;. The 2 HPV-positive tumors showed no alterations in these cell cycle regulators but harbored mutations in &lt;em&gt;PIK3CA&lt;/em&gt;. Other frequently altered genes included &lt;em&gt;KMT2C&lt;/em&gt;&lt;em&gt;/D&lt;/em&gt; (70%), &lt;em&gt;FAT1/&lt;/em&gt;3 (65%), and &lt;em&gt;NOTCH1/2/&lt;/em&gt;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 &gt;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 &lt;em&gt;TERT&lt;/em&gt; 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 &lt;em&gt;TP63&lt;/em&gt; found in 19 tumors.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;In our invasive cSCC cohort, HPV infection was not a major contributor to tumor etiopathogenesis. Our results confirmed the central role of &lt;em&gt;TP53&lt;/em&gt; 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 &lt;em&gt;TERT&lt;/em&gt; 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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Financial Disclosure(s)&lt;/h3&gt;&lt;div&gt;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":"Phase I Study of the Anti-interleukin 33 Fragment Antigen-Binding Region RO7303359 in Geographic Atrophy Secondary to Age-Related Macular Degeneration","authors":"Joel A. Pearlman MD, PhD ,&nbsp;Veeral S. Sheth MD, MBA ,&nbsp;Arshad M. Khanani MD, MA ,&nbsp;Vahan B. Indjeian PhD ,&nbsp;Flavia Brunstein MD, PhD ,&nbsp;Denison Kuruvilla PhD ,&nbsp;Mauricio Maia PhD ,&nbsp;Randall Dere ,&nbsp;Ling Ma PhD ,&nbsp;Hao Chen PhD ,&nbsp;Seema Datta PhD ,&nbsp;Jeffrey R. Willis MD, PhD ,&nbsp;Henry E. Wiley MD","doi":"10.1016/j.xops.2025.100800","DOIUrl":"10.1016/j.xops.2025.100800","url":null,"abstract":"<div><h3>Purpose</h3><div>Interleukin (IL) 33 is a potent proinflammatory cytokine and a potential target in age-related macular degeneration (AMD) pathophysiology. This study evaluated RO7303359, an anti–IL-33 fragment antigen-binding region (Fab) targeting the IL-33/serum stimulation-2 (ST2) pathway, in patients with geographic atrophy (GA) secondary to AMD.</div></div><div><h3>Design</h3><div>Phase I, open-label, multicenter, single-dose, dose-escalation study.</div></div><div><h3>Participants</h3><div>Patients with GA secondary to AMD.</div></div><div><h3>Methods</h3><div>Patients received a single intravitreal (IVT) injection of RO7303359 (dose range, 1–20 mg).</div></div><div><h3>Main Outcome Measures</h3><div>The primary objective was to evaluate the safety and tolerability of RO7303359. The secondary objectives included assessing pharmacokinetics (PK), immune response, and pharmacodynamic (PD) biomarker activity. Pharmacodynamic biomarkers assessed in aqueous humor included CC motif chemokine ligand 2, CXC motif chemokine ligand 10, IL-6, and intercellular adhesion molecule 1.</div></div><div><h3>Results</h3><div>Thirty-seven patients enrolled in the dose cohorts. Single IVT doses of RO7303359 demonstrated an acceptable safety profile up to 20 mg, with mild ocular adverse events reported. Pharmacokinetics analysis revealed dose-proportional exposure within expected ranges for an IVT-administered Fab. No treatment-emergent antidrug antibodies were observed. Evaluation of changes in aqueous humor PD biomarker levels failed to demonstrate a discernible effect on IL-33/ST2 pathway activity.</div></div><div><h3>Conclusions</h3><div>In this trial (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> identifier, NCT04615325), while RO7303359 exhibited acceptable safety and PK profiles, absence of demonstrable effects on the IL-33/ST2 pathway using aqueous PD biomarkers resulted in discontinuation of development in GA. Further work is needed to evaluate the relevance of the IL-33/ST2 pathway in the pathophysiology 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 100800"},"PeriodicalIF":3.2,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230307","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}