Pub Date : 2025-10-15DOI: 10.1016/j.xops.2025.100977
Serena Fragiotta MD, PhD , Giuseppe Querques MD, PhD , Maria Sole Polito MD , Eliana Costanzo MD , Tommaso Rossi MD , Monica Varano MD , Francesca Maria Pannarale MD , Yoichi Sakurada MD , Mariacristina Parravano MD
<div><h3>Purpose</h3><div>Drusenoid pigment epithelial detachment (dPED) is a notable phenotype in age-related macular degeneration (AMD), often evolving into macular complications such as macular neovascularization (MNV) and geographic atrophy (GA). The aim of this study was to identify potential prognostic biomarkers associated with the development of both MNV and GA.</div></div><div><h3>Design</h3><div>A retrospective cohort study.</div></div><div><h3>Participants</h3><div>Patients with dPED in the setting of AMD.</div></div><div><h3>Methods</h3><div>This observational study analyzed OCT biomarkers to assess the dPED lifecycle and identify features predictive of macular complications. Seventy-one eyes with dPED from 51 patients were reviewed over an average follow-up of 37.5 ± 17.6 months (range: 24–104), examining structural alterations via multimodal imaging, which included color fundus photography, fundus autofluorescence, and OCT, while fluorescein angiography, indocyanine green angiography, or both were performed as needed. Associations between baseline biomarkers and macular complications were assessed using Cox proportional hazard models with a frailty term to account for intereye correlation. The Fine–Gray model was used to account for competing risk analysis.</div></div><div><h3>Main Outcome Measures</h3><div>Incidence and time to development of macular complications (MNV and GA) and their associations with baseline OCT biomarkers (cuticular drusen, hyperreflective foci, external limiting membrane/ellipsoid zone integrity, and retinal pigment epithelium [RPE] hypertransmission), modeled with frailty-adjusted Cox proportional hazards and Fine–Gray competing risks; secondary measures included dPED lifecycle features (collapse, timing) and morphometrics (height, width, volume).</div></div><div><h3>Results</h3><div>Key findings included a 39.4% incidence of dPED collapse, with 60.7% of cases progressing to complications postcollapse. In the multivariable Cox proportional model, cuticular drusen (hazard ratio [HR]: 3.8, 95% confidence interval [CI]: 1.62–9.2, <em>P</em> = 0.002) and the presence of hyperreflective foci (HRF) at baseline (HR: 6.6, 95% CI: 1.97–22, <em>P</em> = 0.02) represented the main prognostic indicators of macular complications. In the Fine–Gray competing risks analysis, cuticular drusen remained a significant independent predictor (subdistribution hazard ratio [sHR] = 18.1, 95% CI: 1.89–174, <em>P</em> = 0.01) of MNV development, while HRF (sHR = 6.69, 95% CI: 1.98–22.61, <em>P</em> = 0.002) and external limiting membrane disruption at baseline (sHR = 3.69, 95% CI: 1.03–13.14, <em>P</em> = 0.044) were factors significantly associated with increased GA risk.</div></div><div><h3>Conclusions</h3><div>These results underscore the prognostic relevance of specific imaging biomarkers in dPED. Recognizing these features early may support timely treatment and help prevent irreversible photoreceptor and RPE damage.</div></div><
目的类德鲁素上皮脱离（dPED）是年龄相关性黄斑变性（AMD）的一个显著表型，常演变为黄斑新生血管（MNV）和地理萎缩（GA）等黄斑并发症。本研究的目的是确定与MNV和GA发展相关的潜在预后生物标志物。设计：回顾性队列研究。参与者AMD背景下的dPED患者。方法本观察性研究分析OCT生物标志物来评估dPED的生命周期，并确定预测黄斑并发症的特征。在平均37.5±17.6个月（范围：24-104）的随访期间，对51例dPED患者的71只眼进行了检查，通过多模式成像检查结构改变，包括彩色眼底摄影、眼底自身荧光和OCT，同时根据需要进行荧光素血管造影、吲哚菁绿血管造影或两者兼用。基线生物标志物与黄斑并发症之间的关联使用Cox比例风险模型进行评估，该模型带有一个脆弱项来解释眼间相关性。采用Fine-Gray模型进行竞争风险分析。主要结局指标：黄斑并发症（MNV和GA）的发生率和发展时间及其与基线OCT生物标志物（角质层水肿、高反射灶、外限制膜/椭球带完整性和视网膜色素上皮[RPE]超透射）的关系，采用脆性调整Cox比例风险和Fine-Gray竞争风险建模；次要测量包括dPED生命周期特征（折叠、定时）和形态测量（高度、宽度、体积）。结果dPED塌陷发生率为39.4%，塌陷后并发症发生率为60.7%。在多变量Cox比例模型中，角质层水肿（风险比[HR]: 3.8, 95%可信区间[CI]: 1.62 ~ 9.2, P = 0.002）和基线时是否存在高反射灶（HRF）（风险比：6.6,95% CI: 1.97 ~ 22, P = 0.02）是黄斑并发症的主要预后指标。在细灰色竞争风险分析中，角质层塌陷仍然是MNV发展的重要独立预测因子（亚分布风险比[sHR] = 18.1, 95% CI: 1.89-174, P = 0.01），而HRF （sHR = 6.69, 95% CI: 1.98-22.61, P = 0.002）和基线时外限制性膜破裂（sHR = 3.69, 95% CI: 1.03-13.14, P = 0.044）是与GA风险增加显著相关的因素。结论这些结果强调了特异性成像生物标志物与dPED预后的相关性。早期识别这些特征可能有助于及时治疗，并有助于防止不可逆的感光器和RPE损伤。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":"Structural Biomarkers Influencing Drusenoid Pigment Epithelial Detachment Lifecycle and the Development of Late Macular Degeneration","authors":"Serena Fragiotta MD, PhD , Giuseppe Querques MD, PhD , Maria Sole Polito MD , Eliana Costanzo MD , Tommaso Rossi MD , Monica Varano MD , Francesca Maria Pannarale MD , Yoichi Sakurada MD , Mariacristina Parravano MD","doi":"10.1016/j.xops.2025.100977","DOIUrl":"10.1016/j.xops.2025.100977","url":null,"abstract":"<div><h3>Purpose</h3><div>Drusenoid pigment epithelial detachment (dPED) is a notable phenotype in age-related macular degeneration (AMD), often evolving into macular complications such as macular neovascularization (MNV) and geographic atrophy (GA). The aim of this study was to identify potential prognostic biomarkers associated with the development of both MNV and GA.</div></div><div><h3>Design</h3><div>A retrospective cohort study.</div></div><div><h3>Participants</h3><div>Patients with dPED in the setting of AMD.</div></div><div><h3>Methods</h3><div>This observational study analyzed OCT biomarkers to assess the dPED lifecycle and identify features predictive of macular complications. Seventy-one eyes with dPED from 51 patients were reviewed over an average follow-up of 37.5 ± 17.6 months (range: 24–104), examining structural alterations via multimodal imaging, which included color fundus photography, fundus autofluorescence, and OCT, while fluorescein angiography, indocyanine green angiography, or both were performed as needed. Associations between baseline biomarkers and macular complications were assessed using Cox proportional hazard models with a frailty term to account for intereye correlation. The Fine–Gray model was used to account for competing risk analysis.</div></div><div><h3>Main Outcome Measures</h3><div>Incidence and time to development of macular complications (MNV and GA) and their associations with baseline OCT biomarkers (cuticular drusen, hyperreflective foci, external limiting membrane/ellipsoid zone integrity, and retinal pigment epithelium [RPE] hypertransmission), modeled with frailty-adjusted Cox proportional hazards and Fine–Gray competing risks; secondary measures included dPED lifecycle features (collapse, timing) and morphometrics (height, width, volume).</div></div><div><h3>Results</h3><div>Key findings included a 39.4% incidence of dPED collapse, with 60.7% of cases progressing to complications postcollapse. In the multivariable Cox proportional model, cuticular drusen (hazard ratio [HR]: 3.8, 95% confidence interval [CI]: 1.62–9.2, <em>P</em> = 0.002) and the presence of hyperreflective foci (HRF) at baseline (HR: 6.6, 95% CI: 1.97–22, <em>P</em> = 0.02) represented the main prognostic indicators of macular complications. In the Fine–Gray competing risks analysis, cuticular drusen remained a significant independent predictor (subdistribution hazard ratio [sHR] = 18.1, 95% CI: 1.89–174, <em>P</em> = 0.01) of MNV development, while HRF (sHR = 6.69, 95% CI: 1.98–22.61, <em>P</em> = 0.002) and external limiting membrane disruption at baseline (sHR = 3.69, 95% CI: 1.03–13.14, <em>P</em> = 0.044) were factors significantly associated with increased GA risk.</div></div><div><h3>Conclusions</h3><div>These results underscore the prognostic relevance of specific imaging biomarkers in dPED. Recognizing these features early may support timely treatment and help prevent irreversible photoreceptor and RPE damage.</div></div><","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100977"},"PeriodicalIF":4.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618173","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 latent phenotypic subgroups of diabetic macular edema (DME) using artificial intelligence–based OCT metrics and evaluate whether treatment responses to anti-VEGF and dexamethasone (DEX) therapies differ across these phenotypic clusters.</div></div><div><h3>Methods</h3><div>Retrospective study including 114 eyes (82 patients) with treatment-naïve DME. Quantitative OCT metrics, including intraretinal fluid (IRF) and subretinal fluid volumes, IRF % distribution within central 0–1, 1–3, and 3–6 mm, hyperreflective foci counts, and ellipsoid zone (EZ) % disruption, were analyzed before and after treatment.</div></div><div><h3>Main Outcome Measures</h3><div>Gaussian finite mixture modeling was used to identify distinct DME subgroups. Changes in visual acuity (VA) and OCT parameters following anti-VEGF or DEX therapy were analyzed using linear and generalized linear mixed-effects models, with false discovery rate correction applied to account for multiple comparisons.</div></div><div><h3>Results</h3><div>Three phenotypic clusters of DME were identified, each demonstrating distinct structural and functional characteristics: cluster 1 (29%, 95% confidence interval [CI]: 20.0%–38.4%), characterized by localized central IRF (mean 0.34 mm<sup>3</sup>, 32% in the 0–1 mm zone), moderate structural damage (EZ disruption: 13%), and better VA (mean logarithm of the minimum angle of resolution [LogMAR] 0.29); cluster 2 (49%, 95% CI: 39.6%–57.9%), with diffuse IRF (60% in the 3–6 mm zone), the highest IRF volume (mean: 3.33 mm<sup>3</sup>), significant structural disruption (EZ disruption: 46%), and the poorest VA (mean LogMAR: 0.63); and cluster 3 (22%, 95% CI: 13.9%–31.2%), showing intermediate fluid levels and minimal structural damage (EZ disruption: 0.5%). Anti-VEGF therapy led to the greatest VA improvement in cluster 2 (–31.5%, standard deviation: 28.6). Pairwise contrasts showed no significant VA differences between DEX and anti-VEGF in cluster 1 (–26.6%, 95% CI: –64.7 to 11.6) or in cluster 3 (–12.4%, 95% CI: –58.2 to 33.4), although the direction of effect suggested a trend toward greater improvement with DEX. In contrast, cluster 2 showed a nonsignificant difference favoring anti-VEGF (+25.0%, 95% CI: –4.6 to 54.6). For central subfield thickness, DEX achieved a significantly greater reduction than anti-VEGF in cluster 3 (–20.9%, 95% CI: –37.0 to –4.9) and was also associated with a relative increase in peripheral IRF distribution in cluster 3 (+26.7%, 95% CI: 6.5 to 46.9), supporting phenotype-dependent treatment effects.</div></div><div><h3>Conclusions</h3><div>Latent heterogeneity in DME presentations may influence treatment responses. Artificial intelligence–derived spectral-domain OCT metrics could support tailored therapeutic approaches to optimize patient outcomes.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end
{"title":"What Lies beneath Diabetic Macular Edema: Latent Phenotypic Clustering and Differential Treatment Responses to Intravitreal Therapies","authors":"Maria Vittoria Cicinelli MD , Beatrice Leonardo MDs , Giacomo Maiucci MDs , Giuliano Martino MDs , Makan Ziafati MD , Soufiane Bousyf MD , Luisa Frizziero MD , Rosangela Lattanzio MD , Edoardo Midena MD , Francesco Bandello MD","doi":"10.1016/j.xops.2025.100975","DOIUrl":"10.1016/j.xops.2025.100975","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify latent phenotypic subgroups of diabetic macular edema (DME) using artificial intelligence–based OCT metrics and evaluate whether treatment responses to anti-VEGF and dexamethasone (DEX) therapies differ across these phenotypic clusters.</div></div><div><h3>Methods</h3><div>Retrospective study including 114 eyes (82 patients) with treatment-naïve DME. Quantitative OCT metrics, including intraretinal fluid (IRF) and subretinal fluid volumes, IRF % distribution within central 0–1, 1–3, and 3–6 mm, hyperreflective foci counts, and ellipsoid zone (EZ) % disruption, were analyzed before and after treatment.</div></div><div><h3>Main Outcome Measures</h3><div>Gaussian finite mixture modeling was used to identify distinct DME subgroups. Changes in visual acuity (VA) and OCT parameters following anti-VEGF or DEX therapy were analyzed using linear and generalized linear mixed-effects models, with false discovery rate correction applied to account for multiple comparisons.</div></div><div><h3>Results</h3><div>Three phenotypic clusters of DME were identified, each demonstrating distinct structural and functional characteristics: cluster 1 (29%, 95% confidence interval [CI]: 20.0%–38.4%), characterized by localized central IRF (mean 0.34 mm<sup>3</sup>, 32% in the 0–1 mm zone), moderate structural damage (EZ disruption: 13%), and better VA (mean logarithm of the minimum angle of resolution [LogMAR] 0.29); cluster 2 (49%, 95% CI: 39.6%–57.9%), with diffuse IRF (60% in the 3–6 mm zone), the highest IRF volume (mean: 3.33 mm<sup>3</sup>), significant structural disruption (EZ disruption: 46%), and the poorest VA (mean LogMAR: 0.63); and cluster 3 (22%, 95% CI: 13.9%–31.2%), showing intermediate fluid levels and minimal structural damage (EZ disruption: 0.5%). Anti-VEGF therapy led to the greatest VA improvement in cluster 2 (–31.5%, standard deviation: 28.6). Pairwise contrasts showed no significant VA differences between DEX and anti-VEGF in cluster 1 (–26.6%, 95% CI: –64.7 to 11.6) or in cluster 3 (–12.4%, 95% CI: –58.2 to 33.4), although the direction of effect suggested a trend toward greater improvement with DEX. In contrast, cluster 2 showed a nonsignificant difference favoring anti-VEGF (+25.0%, 95% CI: –4.6 to 54.6). For central subfield thickness, DEX achieved a significantly greater reduction than anti-VEGF in cluster 3 (–20.9%, 95% CI: –37.0 to –4.9) and was also associated with a relative increase in peripheral IRF distribution in cluster 3 (+26.7%, 95% CI: 6.5 to 46.9), supporting phenotype-dependent treatment effects.</div></div><div><h3>Conclusions</h3><div>Latent heterogeneity in DME presentations may influence treatment responses. Artificial intelligence–derived spectral-domain OCT metrics could support tailored therapeutic approaches to optimize patient outcomes.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end ","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100975"},"PeriodicalIF":4.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618170","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 : 2025-10-10DOI: 10.1016/j.xops.2025.100976
Hemal P. Patel MD, Cason B. Robbins MD, Jamie J. Karl MD, Peter Weng MD, PhD, Lejla Vajzovic MD, FASRS, Sharon Fekrat MD, FASRS
{"title":"Corrigendum to “Oral Antithrombotic Medication Is Associated with Improved Visual Outcomes in Eyes with Submacular Hemorrhage from Wet Age-Related Macular Degeneration” [Ophthalmology Science. 2025;5:100796]","authors":"Hemal P. Patel MD, Cason B. Robbins MD, Jamie J. Karl MD, Peter Weng MD, PhD, Lejla Vajzovic MD, FASRS, Sharon Fekrat MD, FASRS","doi":"10.1016/j.xops.2025.100976","DOIUrl":"10.1016/j.xops.2025.100976","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 100976"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925894","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 : 2025-10-10DOI: 10.1016/j.xops.2025.100964
Yun Hsia MD, MS , Hsiao-Lien Chang MD , Tsing-Hong Wang MD, PhD , Jehn-Yu Huang MD, MPH , Chien-Chia Su MD, PhD
Purpose
To investigate the prevalence and types of artifacts in OCT angiography (OCTA) among patients with different glaucoma severities.
Design
Prospective cross-sectional study.
Subjects
Patients with open-angle glaucoma from a tertiary center were prospectively categorized into mild (mean deviation [MD] of 24-2 visual field ≥ –6 decibels [dB]), moderate (–6 to ≥ –12 dB), advanced (–12 to ≥ –20 dB), and severe glaucoma group (MD < –20 dB).
Methods
AngioVue OCTA was performed three times within a single visit to obtain superficial and deep macular vessel density (VD) with 3 x 3–mm macular scans, and peripapillary VD with 4.5 x 4.5–mm scans centered on the optic disc. The intrasession variability was assessed by the coefficient of variation (CoV). Different types of image artifacts were identified.
Main Outcome Measures
The prevalence of artifacts in patients with varying glaucoma severities, patient-related factors associated with artifact occurrence, and their impact on scan quality index (SQI) and variability of OCTA parameters.
Results
Among the 57 mild, 46 moderate, 46 advanced, and 39 severe glaucoma eyes, half of OCTA images exhibited artifacts. Their prevalence increased from 30% in mild to 67% in severe glaucoma (P < 0.001) for peripapillary scans and from 39% to 62% (P = 0.001) for macular scans. Defocus was the most common artifact (26%) and increased with worsening MD (P = 0.006), contributing to greater CoV of superficial (P = 0.043) and deep (P = 0.024) macular VD and reduced macular SQI (P = 0.018). Peripapillary scans were more affected by artifacts, with defocus (P < 0.001) and eye movement (P = 0.025) increasing as MD worsened, which reduced the peripapillary SQI (P = 0.003 and P < 0.001, respectively). Lower SQI (P < 0.001), eye movement (P = 0.042), and quilt (P = 0.047) were linked to greater CoV of peripapillary VD.
Conclusions
Defocus is the most common OCTA artifact in glaucoma patients, increasing variability in OCTA metrics. Its prevalence rises with glaucoma severity and remains high even in scans with acceptable image quality, emphasizing the need for careful artifact assessment.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any materials discussed in this article.
{"title":"The Artifacts in Macular and Peripapillary OCT Angiography in Patients with Different Severities of Glaucoma","authors":"Yun Hsia MD, MS , Hsiao-Lien Chang MD , Tsing-Hong Wang MD, PhD , Jehn-Yu Huang MD, MPH , Chien-Chia Su MD, PhD","doi":"10.1016/j.xops.2025.100964","DOIUrl":"10.1016/j.xops.2025.100964","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the prevalence and types of artifacts in OCT angiography (OCTA) among patients with different glaucoma severities.</div></div><div><h3>Design</h3><div>Prospective cross-sectional study.</div></div><div><h3>Subjects</h3><div>Patients with open-angle glaucoma from a tertiary center were prospectively categorized into mild (mean deviation [MD] of 24-2 visual field ≥ –6 decibels [dB]), moderate (–6 to ≥ –12 dB), advanced (–12 to ≥ –20 dB), and severe glaucoma group (MD < –20 dB).</div></div><div><h3>Methods</h3><div>AngioVue OCTA was performed three times within a single visit to obtain superficial and deep macular vessel density (VD) with 3 x 3–mm macular scans, and peripapillary VD with 4.5 x 4.5–mm scans centered on the optic disc. The intrasession variability was assessed by the coefficient of variation (CoV). Different types of image artifacts were identified.</div></div><div><h3>Main Outcome Measures</h3><div>The prevalence of artifacts in patients with varying glaucoma severities, patient-related factors associated with artifact occurrence, and their impact on scan quality index (SQI) and variability of OCTA parameters.</div></div><div><h3>Results</h3><div>Among the 57 mild, 46 moderate, 46 advanced, and 39 severe glaucoma eyes, half of OCTA images exhibited artifacts. Their prevalence increased from 30% in mild to 67% in severe glaucoma (<em>P</em> < 0.001) for peripapillary scans and from 39% to 62% (<em>P</em> = 0.001) for macular scans. Defocus was the most common artifact (26%) and increased with worsening MD (<em>P</em> = 0.006), contributing to greater CoV of superficial (<em>P</em> = 0.043) and deep (<em>P</em> = 0.024) macular VD and reduced macular SQI (<em>P</em> = 0.018). Peripapillary scans were more affected by artifacts, with defocus (<em>P</em> < 0.001) and eye movement (<em>P</em> = 0.025) increasing as MD worsened, which reduced the peripapillary SQI (<em>P</em> = 0.003 and <em>P</em> < 0.001, respectively). Lower SQI (<em>P</em> < 0.001), eye movement (<em>P</em> = 0.042), and quilt (<em>P</em> = 0.047) were linked to greater CoV of peripapillary VD.</div></div><div><h3>Conclusions</h3><div>Defocus is the most common OCTA artifact in glaucoma patients, increasing variability in OCTA metrics. Its prevalence rises with glaucoma severity and remains high even in scans with acceptable image quality, emphasizing the need for careful artifact assessment.</div></div><div><h3>Financial Disclosure(s)</h3><div>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 1","pages":"Article 100964"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618260","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}
In total, 142 eyes were included in the study: 72 in the RP group and 70 in the control group. Global pRNFL thicknesses were 89.3 ± 38.9, 86.5 ± 35.2, 84.6 ± 31.8, and 81.6 ± 31.3 μm at baseline, 1 year, 2 years, and 3 years in the RP group (P = 0.022), and 100.9 ± 6.3, 100.8 ± 7.0, 100.0 ± 6.3, and 100.3 ± 6.9 μm in the control group ( = 0.079), respectively. The reduction rate of pRNFL thickness was –2.45 μm/y in the RP group and –0.25 μm/y in the control group. In multivariate analysis, age (estimate = –0.55, P = 0.021) and RP stage (estimate = –15.42, P = 0.005) were significant factors associated with changes in pRNFL thickness in RP patients.
Conclusions
Retinitis pigmentosa patients exhibited a thinner pRNFL and a faster rate of thinning over time compared with healthy controls. In RP patients, pRNFL thinning was significantly associated with age and disease stage, possibly reflecting accelerated damage with disease progression.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any materials discussed in this article.
{"title":"Longitudinal Changes in Peripapillary Retinal Nerve Fiber Layer Thickness in Patients with Retinitis Pigmentosa","authors":"Jae-Yun Sung MD, PhD , Jung-Tae Kim MD, PhD , Yun-Sang Roh MD , Min-Woo Lee MD, PhD","doi":"10.1016/j.xops.2025.100966","DOIUrl":"10.1016/j.xops.2025.100966","url":null,"abstract":"<div><h3>Purpose</h3><div>To perform a longitudinal analysis of peripapillary retinal nerve fiber layer (pRNFL) thickness in retinitis pigmentosa (RP) patients.</div></div><div><h3>Design</h3><div>A retrospective, longitudinal study.</div></div><div><h3>Subjects</h3><div>We enrolled patients diagnosed with RP and normal controls.</div></div><div><h3>Methods</h3><div>After the baseline visit, 3 additional measurements of pRNFL thickness at 1-year intervals were analyzed.</div></div><div><h3>Main Outcome Measures</h3><div>Peripapillary retinal nerve fiber layer thickness.</div></div><div><h3>Results</h3><div>In total, 142 eyes were included in the study: 72 in the RP group and 70 in the control group. Global pRNFL thicknesses were 89.3 ± 38.9, 86.5 ± 35.2, 84.6 ± 31.8, and 81.6 ± 31.3 μm at baseline, 1 year, 2 years, and 3 years in the RP group (<em>P</em> = 0.022), and 100.9 ± 6.3, 100.8 ± 7.0, 100.0 ± 6.3, and 100.3 ± 6.9 μm in the control group ( = 0.079), respectively. The reduction rate of pRNFL thickness was –2.45 μm/y in the RP group and –0.25 μm/y in the control group. In multivariate analysis, age (estimate = –0.55, <em>P</em> = 0.021) and RP stage (estimate = –15.42, <em>P</em> = 0.005) were significant factors associated with changes in pRNFL thickness in RP patients.</div></div><div><h3>Conclusions</h3><div>Retinitis pigmentosa patients exhibited a thinner pRNFL and a faster rate of thinning over time compared with healthy controls. In RP patients, pRNFL thinning was significantly associated with age and disease stage, possibly reflecting accelerated damage with disease progression.</div></div><div><h3>Financial Disclosure(s)</h3><div>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 1","pages":"Article 100966"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145579184","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}
To assess the efficacy and safety of orally administered calpain inhibitor SJP-0008 in Japanese patients with central retinal artery occlusion (CRAO), to establish a disease registry for the prospective tracking of observational data from patients with CRAO, intended for regulatory use, and to support the development of new therapeutic agents for CRAO.
Design
This was a 2-part study. Part 1 was a physician-/investigator-initiated, phase IIa, single-center, randomized, double-blinded, parallel-group study. Part 2 was a prospective cohort study, during which the CRAO registry was established, and included patients diagnosed with CRAO (including a nonrandomized registry cohort, the non-SJP group, which did not receive SJP-0008). Additionally, in part 2, a combined analysis was performed using data from part 1 patients.
Participants
The study participants were patients recruited within 48 hours of developing CRAO.
Methods
SJP-0008 administration was initiated at least 3 hours but no more than 48 hours after the onset of CRAO. Patients were randomized in a 1:1 ratio using masked randomization to receive either 100-mg or 200-mg doses of SJP-0008. The dosing period was defined as the 4-week postinitiation period (up to 29 days), followed by an 8-week postobservation phase.
Main Outcome Measures
The main outcome measure was to determine the efficacy of SJP-0008 treatment; the primary endpoint was the change in ETDRS visual acuity at 12 weeks in the target eye of patients with CRAO.
Results
The study included 28 patients (mean age: 68.8 ± 14.9 years; 78.6% male). ETDRS scores (mean [95% confidence interval]) were higher at week 12 than at baseline in both the 100-mg (27.9 letters [10.14, 45.61]) and 200-mg (25.7 letters [12.02, 39.40]) SJP-0008 groups, in contrast to the non-SJP group (10.2 letters [4.58, 15.76]). The improvement in the 200-mg SJP-0008 group was greater than in the nonrandomized non-SJP group (P = 0.040). No safety concerns were identified.
Conclusions
The preliminary study supports the safety and efficacy of oral administration of SJP-0008 for treating CRAO, with greater improvement compared with the nonrandomized registry cohort. However, large-scale, multicenter randomized controlled trials are warranted to validate the findings of this study.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Safety and Efficacy of Orally Administered SJP-0008 in Central Retinal Artery Occlusion: A Phase IIa Randomized Clinical Trial","authors":"Satoru Tsuda MD, PhD , Hiroshi Kunikata MD, PhD , Kazuki Hashimoto MD, PhD , Toshifumi Asano MD, PhD , Azusa Ito MD, PhD , Mitsuhide Yoshida DDS, PhD , Masayuki Yasuda MD, PhD , Fumihiko Nitta MD, PhD , Toru Nakazawa MD, PhD","doi":"10.1016/j.xops.2025.100965","DOIUrl":"10.1016/j.xops.2025.100965","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the efficacy and safety of orally administered calpain inhibitor SJP-0008 in Japanese patients with central retinal artery occlusion (CRAO), to establish a disease registry for the prospective tracking of observational data from patients with CRAO, intended for regulatory use, and to support the development of new therapeutic agents for CRAO.</div></div><div><h3>Design</h3><div>This was a 2-part study. Part 1 was a physician-/investigator-initiated, phase IIa, single-center, randomized, double-blinded, parallel-group study. Part 2 was a prospective cohort study, during which the CRAO registry was established, and included patients diagnosed with CRAO (including a nonrandomized registry cohort, the non-SJP group, which did not receive SJP-0008). Additionally, in part 2, a combined analysis was performed using data from part 1 patients.</div></div><div><h3>Participants</h3><div>The study participants were patients recruited within 48 hours of developing CRAO.</div></div><div><h3>Methods</h3><div>SJP-0008 administration was initiated at least 3 hours but no more than 48 hours after the onset of CRAO. Patients were randomized in a 1:1 ratio using masked randomization to receive either 100-mg or 200-mg doses of SJP-0008. The dosing period was defined as the 4-week postinitiation period (up to 29 days), followed by an 8-week postobservation phase.</div></div><div><h3>Main Outcome Measures</h3><div>The main outcome measure was to determine the efficacy of SJP-0008 treatment; the primary endpoint was the change in ETDRS visual acuity at 12 weeks in the target eye of patients with CRAO.</div></div><div><h3>Results</h3><div>The study included 28 patients (mean age: 68.8 ± 14.9 years; 78.6% male). ETDRS scores (mean [95% confidence interval]) were higher at week 12 than at baseline in both the 100-mg (27.9 letters [10.14, 45.61]) and 200-mg (25.7 letters [12.02, 39.40]) SJP-0008 groups, in contrast to the non-SJP group (10.2 letters [4.58, 15.76]). The improvement in the 200-mg SJP-0008 group was greater than in the nonrandomized non-SJP group (<em>P</em> = 0.040). No safety concerns were identified.</div></div><div><h3>Conclusions</h3><div>The preliminary study supports the safety and efficacy of oral administration of SJP-0008 for treating CRAO, with greater improvement compared with the nonrandomized registry cohort. However, large-scale, multicenter randomized controlled trials are warranted to validate the findings of this study.</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 1","pages":"Article 100965"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519899","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 : 2025-10-10DOI: 10.1016/j.xops.2025.100967
Jizhou Tian MS , Diep Tran MS , Zainab Rustam MBBS , Gina Zhu BS , Paul Nagy PhD , Hadi Kharrazi MD, PhD , Deidra C. Crews MD, ScM , Zitong Wang PhD , Scott L. Zeger PhD , Cindy X. Cai MD, MS
Objective
To predict lapses in diabetic retinopathy (DR) care.
Design
Retrospective cohort study.
Subjects
Adults ≥18 years with diabetes seen at the Wilmer Eye Institute for DR screening or treatment between 2012 and 2022.
Main Outcome Measures
Whether an office visit for DR screening or treatment was followed by a lapse in care.
Methods
Three versions of prediction algorithms were constructed using random forests (RFs). XGBoost (XGB) was used as a confirmatory analysis. Random forest-A and XGB-A included electronic health record (EHR) variables alone (e.g., sociodemographic, insurance, ophthalmic diagnoses, lead time, and recommended follow-up time). Random forest-B and XGB-B added location-based social determinants of health (SDoH) variables (e.g., Area Deprivation Index). Random forest-C and XGB-C added history of lapses in care (e.g., whether the patient has ever had lapses in care before). The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) were calculated for each algorithm.
Results
A total of 36 995 patients (mean age 62 years, 53% female, 47% non-Hispanic White, 38% non-Hispanic Black, and 4% Hispanic) and 141 930 office visits were included. The best performing model was RF-C with an AUROC of 0.774 (0.772–0.776) and AUPRC of 0.707 (0.704–0.711), outperforming RF-A and RF-B in AUROC and AUPRC (P < 0.001 for each comparison). XGB-C similarly outperformed XGB-A and XGB-B (P < 0.001 for each comparison).
Conclusions
We developed RF algorithms, as well as XGB confirmatory models, to predict whether patients with diabetes will experience a lapse in DR care. The best prediction was achieved using EHR variables, location-based SDoH variables, and history of lapses in care. These models offer the opportunity to identify high-risk patients and offer additional resources to reduce lapses in care and potentially vision loss from DR.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Identifying Patients at High Risk of Lapses in Diabetic Retinopathy Care: A Machine Learning Study","authors":"Jizhou Tian MS , Diep Tran MS , Zainab Rustam MBBS , Gina Zhu BS , Paul Nagy PhD , Hadi Kharrazi MD, PhD , Deidra C. Crews MD, ScM , Zitong Wang PhD , Scott L. Zeger PhD , Cindy X. Cai MD, MS","doi":"10.1016/j.xops.2025.100967","DOIUrl":"10.1016/j.xops.2025.100967","url":null,"abstract":"<div><h3>Objective</h3><div>To predict lapses in diabetic retinopathy (DR) care.</div></div><div><h3>Design</h3><div>Retrospective cohort study.</div></div><div><h3>Subjects</h3><div>Adults ≥18 years with diabetes seen at the Wilmer Eye Institute for DR screening or treatment between 2012 and 2022.</div></div><div><h3>Main Outcome Measures</h3><div>Whether an office visit for DR screening or treatment was followed by a lapse in care.</div></div><div><h3>Methods</h3><div>Three versions of prediction algorithms were constructed using random forests (RFs). XGBoost (XGB) was used as a confirmatory analysis. Random forest-A and XGB-A included electronic health record (EHR) variables alone (e.g., sociodemographic, insurance, ophthalmic diagnoses, lead time, and recommended follow-up time). Random forest-B and XGB-B added location-based social determinants of health (SDoH) variables (e.g., Area Deprivation Index). Random forest-C and XGB-C added history of lapses in care (e.g., whether the patient has ever had lapses in care before). The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) were calculated for each algorithm.</div></div><div><h3>Results</h3><div>A total of 36 995 patients (mean age 62 years, 53% female, 47% non-Hispanic White, 38% non-Hispanic Black, and 4% Hispanic) and 141 930 office visits were included. The best performing model was RF-C with an AUROC of 0.774 (0.772–0.776) and AUPRC of 0.707 (0.704–0.711), outperforming RF-A and RF-B in AUROC and AUPRC (<em>P</em> < 0.001 for each comparison). XGB-C similarly outperformed XGB-A and XGB-B (<em>P</em> < 0.001 for each comparison).</div></div><div><h3>Conclusions</h3><div>We developed RF algorithms, as well as XGB confirmatory models, to predict whether patients with diabetes will experience a lapse in DR care. The best prediction was achieved using EHR variables, location-based SDoH variables, and history of lapses in care. These models offer the opportunity to identify high-risk patients and offer additional resources to reduce lapses in care and potentially vision loss from DR.</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 1","pages":"Article 100967"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466347","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 : 2025-10-10DOI: 10.1016/j.xops.2025.100971
Elise Rochet PhD , Feargal J. Ryan PhD , Yuefang Ma PhD , Liam M. Ashander BS , Shashikanth Marri PhD , Janet M. Matthews BS , João M. Furtado MD, PhD , Binoy Appukuttan PhD , David J. Lynn PhD , Justine R. Smith FRANZCO, PhD
Purpose
Ocular toxoplasmosis, caused by infection with Toxoplasma gondii, is characterized by retinal necrosis and reactive intraocular inflammation. Müller glial cells are a principal retinal host cell population for T. gondii. The goal of this research was to delineate potential involvements of Müller glial cells in ocular toxoplasmosis at a molecular level.
Design
Laboratory-based study.
Samples
Human retinal Müller glial cells infected with T. gondii plus noninfected cells.
Methods
Monolayers of Müller glial cells isolated from human retina (6 donor eye pairs) were infected for 24 hours with GT1 or GPHT strain T. gondii tachyzoites (multiplicity of infection of 5), or incubated in parallel without infection. Total RNA and small RNA were extracted from cell monolayers, sequenced on the Illumina NovaSeq 6000 and NextSeq 550 platforms, respectively, and aligned to GRCh38. Transcriptomic responses to infection with each strain were compared for differential expression (false discovery rate <5% and twofold change). These data were interrogated for enrichment of Reactome and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Gene Ontology in InnateDB; putative transcription factor binding sites in HOMER; and potential microRNA–mRNA interactions in multiMiR.
Main Outcome Measures
Total and small RNA transcriptomes.
Results
6.3% of total RNA and 2.4% of small RNA changed in GT1-infected cells (582 upregulated and 210 downregulated transcripts and 20 upregulated microRNAs) versus 4.3% of total RNA and 1.5% of small RNA in GPHT-infected cells (400 upregulated and 137 downregulated transcripts and 12 upregulated microRNAs). Seventy-six transcripts and 4 microRNAs were different between strains; most were increased by both, but GT1 induced higher levels than GPHT. Enriched pathways and ontologies were dominated by DNA replication and intracellular metabolic activities, and the immune response for GT1 and GPHT. Seven of 8 transcription factor binding sites were shared for GT1 and GPHT infections, all overexpressed, including sites for p65/RELA and E2F family members. Across the strains, miR-18a-5p was the most connected microRNA in predicted mRNA target networks.
Conclusions
This work demonstrates that human retinal Müller glial cells shift to a proliferative and inflammatory phenotype when infected with T. gondii tachyzoites, consistent with a central role in the characteristic pathology of ocular toxoplasmosis.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Total RNA and MicroRNA Transcriptomic Responses of Human Retinal Müller Glial Cells to Infection with Toxoplasma gondii Tachyzoites","authors":"Elise Rochet PhD , Feargal J. Ryan PhD , Yuefang Ma PhD , Liam M. Ashander BS , Shashikanth Marri PhD , Janet M. Matthews BS , João M. Furtado MD, PhD , Binoy Appukuttan PhD , David J. Lynn PhD , Justine R. Smith FRANZCO, PhD","doi":"10.1016/j.xops.2025.100971","DOIUrl":"10.1016/j.xops.2025.100971","url":null,"abstract":"<div><h3>Purpose</h3><div>Ocular toxoplasmosis, caused by infection with <em>Toxoplasma gondii</em>, is characterized by retinal necrosis and reactive intraocular inflammation. Müller glial cells are a principal retinal host cell population for <em>T. gondii</em>. The goal of this research was to delineate potential involvements of Müller glial cells in ocular toxoplasmosis at a molecular level.</div></div><div><h3>Design</h3><div>Laboratory-based study.</div></div><div><h3>Samples</h3><div>Human retinal Müller glial cells infected with <em>T. gondii</em> plus noninfected cells.</div></div><div><h3>Methods</h3><div>Monolayers of Müller glial cells isolated from human retina (6 donor eye pairs) were infected for 24 hours with GT1 or GPHT strain <em>T. gondii</em> tachyzoites (multiplicity of infection of 5), or incubated in parallel without infection. Total RNA and small RNA were extracted from cell monolayers, sequenced on the Illumina NovaSeq 6000 and NextSeq 550 platforms, respectively, and aligned to GRCh38. Transcriptomic responses to infection with each strain were compared for differential expression (false discovery rate <5% and twofold change). These data were interrogated for enrichment of Reactome and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Gene Ontology in InnateDB; putative transcription factor binding sites in HOMER; and potential microRNA–mRNA interactions in multiMiR.</div></div><div><h3>Main Outcome Measures</h3><div>Total and small RNA transcriptomes.</div></div><div><h3>Results</h3><div>6.3% of total RNA and 2.4% of small RNA changed in GT1-infected cells (582 upregulated and 210 downregulated transcripts and 20 upregulated microRNAs) versus 4.3% of total RNA and 1.5% of small RNA in GPHT-infected cells (400 upregulated and 137 downregulated transcripts and 12 upregulated microRNAs). Seventy-six transcripts and 4 microRNAs were different between strains; most were increased by both, but GT1 induced higher levels than GPHT. Enriched pathways and ontologies were dominated by DNA replication and intracellular metabolic activities, and the immune response for GT1 and GPHT. Seven of 8 transcription factor binding sites were shared for GT1 and GPHT infections, all overexpressed, including sites for p65/RELA and E2F family members. Across the strains, miR-18a-5p was the most connected microRNA in predicted mRNA target networks.</div></div><div><h3>Conclusions</h3><div>This work demonstrates that human retinal Müller glial cells shift to a proliferative and inflammatory phenotype when infected with <em>T. gondii</em> tachyzoites, consistent with a central role in the characteristic pathology of ocular toxoplasmosis.</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 1","pages":"Article 100971"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789917","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 : 2025-10-10DOI: 10.1016/j.xops.2025.100974
Peter W. Hunt MD , Adam B. Olshen PhD , Natalia Murad PhD , Gabrielle C. Ambayec BS , Efe Sezgin PhD , Michael F. Schneider MS , Douglas A. Jabs MD, MBA
{"title":"Erratum to “Plasma Proteomic Markers of Interleukin-1β Pathway Associated with Incident Age-Related Macular Degeneration in Persons with AIDS” [Ophthalmol Sci. 2025;5:100794]","authors":"Peter W. Hunt MD , Adam B. Olshen PhD , Natalia Murad PhD , Gabrielle C. Ambayec BS , Efe Sezgin PhD , Michael F. Schneider MS , Douglas A. Jabs MD, MBA","doi":"10.1016/j.xops.2025.100974","DOIUrl":"10.1016/j.xops.2025.100974","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 100974"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976576","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: Pushpanathan et al.: Can OpenAI’s New o1 Model Outperform Its Predecessors in Common Eye Care Queries?","authors":"Yusuke Kameda MD, PhD , Yutaka Kaneko MD, PhD , Saki Takada","doi":"10.1016/j.xops.2025.100968","DOIUrl":"10.1016/j.xops.2025.100968","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100968"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466348","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}
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