Pub Date : 2025-08-20DOI: 10.1016/j.xops.2025.100921
Zi Xuan Lin MMed , Fangyao Tang PhD , Xiu Juan Zhang PhD , Xiunian Chen MMed , Yuzhou Zhang PhD , Simon K.H. Szeto FCOphthaHK , Wei Zhang MD, PhD , Danny S.C. Ng MPH, FRCSEd , Ka Wai Kam MSc , Alvin L. Young MMedSc , Clement C. Tham BM BCH, FRCOphth , Chi Pui Pang DPhil , Li Jia Chen PhD, FCOphthHK , Jason C. Yam MD, FRCSEd
Topic
This study systematically evaluates changes in retinal and choroidal microvasculature with increasing myopia severity.
Clinical Relevance
Conflicting results in reported studies on the changes in retinal and choroidal microvasculature with increasing myopia severity require comprehensive analysis to guide patient management.
Methods
The PubMed, Embase, and Web of Science databases were thoroughly searched for studies published before May 8, 2025 on retinal or choroidal changes across different myopia severities. Included were studies with cross-sectional or prospective case-control and cohort designs that reported outcomes of foveal avascular zone (FAZ) area and vessel densities (VD) in the retina and choroid. The risk of bias was assessed by the Newcastle–Ottawa Scale and the Agency for Healthcare Research and Quality tools. Funnel plot with Egger test assessed potential publication bias. Meta-regressions were conducted to identify potential moderators in subgroup meta-analyses with high heterogeneity. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42023402550.
Results
A total of 47 studies comprising 7293 eyes were included. Highly myopic eyes demonstrated significantly enlarged FAZ area in both the superficial capillary plexus (SCP) (P = 0.049, standard mean difference [SMD]: 0.37, 95% confidence interval [CI]: [0.00, 0.74], I2 = 82%) and deep capillary plexus (DCP) (P = 0.001, SMD: 0.61, 95% CI: [0.24, 0.98], I2 = 83%). Macular VD was significantly reduced in the SCP for moderate and high myopia (HM) subgroups (P = 0.003 and P < 0.001, respectively) and in the DCP for the HM subgroup (P < 0.001). Significant VD reductions were also observed in parafoveal (SCP: P < 0.001, DCP: P = 0.012) and perifoveal (SCP: P = 0.006; DCP: P < 0.001) regions in the HM subgroup in both plexuses. Peripapillary VD showed consistent reductions across mild, moderate, and HM subgroups (all P ≤ 0.033). No significant differences were observed in choriocapillaris VD or flow area.
Conclusions
This meta-analysis revealed significantly enlarged FAZ areas and reduced VD in the macular and peripapillary regions with increasing myopia, especially in HM. These findings enhance the understanding of myopia-related fundus microvascular changes, guiding the clinical management and screening of patients with HM.
本研究系统评估视网膜和脉络膜微血管随近视严重程度增加的变化。关于视网膜和脉络膜微血管随近视严重程度增加而变化的研究报告结果相互矛盾，需要综合分析以指导患者管理。方法全面检索PubMed、Embase和Web of Science数据库，检索2025年5月8日之前发表的关于不同近视严重程度视网膜或脉络膜变化的研究。纳入了横断面或前瞻性病例对照和队列设计的研究，这些研究报告了视网膜和脉络膜中央凹无血管区（FAZ）面积和血管密度（VD）的结果。偏倚风险通过纽卡斯尔-渥太华量表和医疗保健研究与质量机构工具进行评估。用Egger检验的漏斗图评估潜在的发表偏倚。进行meta回归以确定具有高异质性的亚组meta分析中的潜在调节因子。该方案已在国际前瞻性系统评价登记册（PROSPERO）注册：CRD42023402550。结果共纳入47项研究，7293只眼。高度近视眼在浅毛细血管丛（SCP） （P = 0.049，标准平均差[SMD]: 0.37, 95%可信区间[CI]: [0.00, 0.74], I2 = 82%）和深毛细血管丛（DCP） （P = 0.001, SMD: 0.61, 95% CI: [0.24, 0.98], I2 = 83%）的FAZ面积均显著增大。中度和高度近视（HM）亚组（P = 0.003和P <； 0.001）和高度近视（HM）亚组（P < 0.001）的DCP组黄斑VD显著降低。在两个神经丛HM亚组的凹旁区（SCP: P < 0.001, DCP: P = 0.012）和凹周围区（SCP: P = 0.006, DCP: P < 0.001）也观察到明显的VD减少。乳头周围VD在轻度、中度和HM亚组中均显示一致的减少（均P≤0.033）。绒毛膜毛细血管VD和血流面积无显著差异。结论本荟萃分析显示，随着近视的增加，黄斑和乳头周围区域的FAZ面积显著增加，VD显著降低，尤其是HM。这些发现有助于加深对近视相关眼底微血管变化的认识，指导HM患者的临床管理和筛查。
{"title":"Retinal and Choroidal Microvasculature at Different Myopia Severities: A Systematic Review and Meta-Analysis","authors":"Zi Xuan Lin MMed , Fangyao Tang PhD , Xiu Juan Zhang PhD , Xiunian Chen MMed , Yuzhou Zhang PhD , Simon K.H. Szeto FCOphthaHK , Wei Zhang MD, PhD , Danny S.C. Ng MPH, FRCSEd , Ka Wai Kam MSc , Alvin L. Young MMedSc , Clement C. Tham BM BCH, FRCOphth , Chi Pui Pang DPhil , Li Jia Chen PhD, FCOphthHK , Jason C. Yam MD, FRCSEd","doi":"10.1016/j.xops.2025.100921","DOIUrl":"10.1016/j.xops.2025.100921","url":null,"abstract":"<div><h3>Topic</h3><div>This study systematically evaluates changes in retinal and choroidal microvasculature with increasing myopia severity.</div></div><div><h3>Clinical Relevance</h3><div>Conflicting results in reported studies on the changes in retinal and choroidal microvasculature with increasing myopia severity require comprehensive analysis to guide patient management.</div></div><div><h3>Methods</h3><div>The PubMed, Embase, and Web of Science databases were thoroughly searched for studies published before May 8, 2025 on retinal or choroidal changes across different myopia severities. Included were studies with cross-sectional or prospective case-control and cohort designs that reported outcomes of foveal avascular zone (FAZ) area and vessel densities (VD) in the retina and choroid. The risk of bias was assessed by the Newcastle–Ottawa Scale and the Agency for Healthcare Research and Quality tools. Funnel plot with Egger test assessed potential publication bias. Meta-regressions were conducted to identify potential moderators in subgroup meta-analyses with high heterogeneity. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42023402550.</div></div><div><h3>Results</h3><div>A total of 47 studies comprising 7293 eyes were included. Highly myopic eyes demonstrated significantly enlarged FAZ area in both the superficial capillary plexus (SCP) (<em>P</em> = 0.049, standard mean difference [SMD]: 0.37, 95% confidence interval [CI]: [0.00, 0.74], I<sup>2</sup> = 82%) and deep capillary plexus (DCP) (<em>P</em> = 0.001, SMD: 0.61, 95% CI: [0.24, 0.98], I<sup>2</sup> = 83%). Macular VD was significantly reduced in the SCP for moderate and high myopia (HM) subgroups (<em>P</em> = 0.003 and <em>P</em> < 0.001, respectively) and in the DCP for the HM subgroup (<em>P</em> < 0.001). Significant VD reductions were also observed in parafoveal (SCP: <em>P</em> < 0.001, DCP: <em>P</em> = 0.012) and perifoveal (SCP: <em>P</em> = 0.006; DCP: <em>P</em> < 0.001) regions in the HM subgroup in both plexuses. Peripapillary VD showed consistent reductions across mild, moderate, and HM subgroups (all <em>P</em> ≤ 0.033). No significant differences were observed in choriocapillaris VD or flow area.</div></div><div><h3>Conclusions</h3><div>This meta-analysis revealed significantly enlarged FAZ areas and reduced VD in the macular and peripapillary regions with increasing myopia, especially in HM. These findings enhance the understanding of myopia-related fundus microvascular changes, guiding the clinical management and screening of patients with HM.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100921"},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222741","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 : 2025-08-20DOI: 10.1016/j.xops.2025.100919
Jason Y. Zhang MD , Deborah S. Bondi PharmD , Max J. Hyman BA , Dimitra Skondra MD, PhD , Simmer Beniwal BS, MPH , John Moir MD , Sarah H. Rodriguez MD, MPH
Objective
Retinopathy of prematurity (ROP) has been linked to neonatal sepsis, with antibiotic use suggested as a connection. Given the role of antibiotics in gut dysbiosis and the gut–retina axis, we assessed whether exposure to different antibiotic classes is associated with the incidence of treatment-necessary ROP.
Design
Retrospective cohort study.
Subjects
Preterm infants born at the University of Chicago Medicine and screened for ROP between January 2012 and December 2023.
Methods
Retrospective analysis was performed to compare systemic antibiotic exposure within the first 2 months of life between infants with type 1 ROP (ie, required treatment) and those that did not require treatment. Multivariable adjustment included birth weight (BW), gestational age (GA), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, necrotizing enterocolitis (NEC), and neonatal sepsis. To reduce potential confounding by indication, propensity score matching was performed.
Main Outcome Measures
Type 1 ROP by systemic exposure to antibiotic classes.
Results
Seven hundred twenty infants were included, with 50 treated for ROP. The rate of systemic antibiotic use was 97.3% in the control group and 100.0% in infants with type 1 ROP. Infants with type 1 ROP showed higher rates of BPD (P < 0.001) and bacterial infection (P = 0.007). No association was noted with NEC. In multivariable regression, the odds of treatment were significantly greater for infants receiving cephalosporins, carbapenems, and monobactams (odds ratio [OR], 4.25; 95% confidence interval [CI], 1.74–10.4; P = 0.002), and an exploratory analysis suggested a dose-response per day prescribed (OR, 1.07; 95% CI, 1.03–1.11; P = 0.001). When restricted to BW <750 g or GA <27 weeks (N = 259, with 49 treated for ROP), these associations remained significant (OR, 3.87; 95% CI, 1.57–9.51; P = 0.003; per day prescribed: OR, 1.07; 95% CI, 1.03–1.11; P = 0.001). After propensity score matching for BW, GA, BPD, sepsis, and any bacterial infection, the average percent of infants who required treatment was 9.9 percentage points higher among those who received cephalosporins, carbapenems, and monobactams compared to those same infants if they had not received them (95% CI, 2.0–17.8 percentage points; P = 0.014).
Conclusions
Early exposure to broad-spectrum antibiotic classes, particularly cephalosporins, carbapenems, and monobactams, may be associated with type 1 ROP.
Financial Disclosure(s)
The authors has no/the authors have no proprietary or commercial interest in any materials discussed in this article.
{"title":"Early Antibiotic Use and Retinopathy of Prematurity: A Single-Center Retrospective Cohort Study","authors":"Jason Y. Zhang MD , Deborah S. Bondi PharmD , Max J. Hyman BA , Dimitra Skondra MD, PhD , Simmer Beniwal BS, MPH , John Moir MD , Sarah H. Rodriguez MD, MPH","doi":"10.1016/j.xops.2025.100919","DOIUrl":"10.1016/j.xops.2025.100919","url":null,"abstract":"<div><h3>Objective</h3><div>Retinopathy of prematurity (ROP) has been linked to neonatal sepsis, with antibiotic use suggested as a connection. Given the role of antibiotics in gut dysbiosis and the gut–retina axis, we assessed whether exposure to different antibiotic classes is associated with the incidence of treatment-necessary ROP.</div></div><div><h3>Design</h3><div>Retrospective cohort study.</div></div><div><h3>Subjects</h3><div>Preterm infants born at the University of Chicago Medicine and screened for ROP between January 2012 and December 2023.</div></div><div><h3>Methods</h3><div>Retrospective analysis was performed to compare systemic antibiotic exposure within the first 2 months of life between infants with type 1 ROP (ie, required treatment) and those that did not require treatment. Multivariable adjustment included birth weight (BW), gestational age (GA), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, necrotizing enterocolitis (NEC), and neonatal sepsis. To reduce potential confounding by indication, propensity score matching was performed.</div></div><div><h3>Main Outcome Measures</h3><div>Type 1 ROP by systemic exposure to antibiotic classes.</div></div><div><h3>Results</h3><div>Seven hundred twenty infants were included, with 50 treated for ROP. The rate of systemic antibiotic use was 97.3% in the control group and 100.0% in infants with type 1 ROP. Infants with type 1 ROP showed higher rates of BPD (<em>P</em> < 0.001) and bacterial infection (<em>P</em> = 0.007). No association was noted with NEC. In multivariable regression, the odds of treatment were significantly greater for infants receiving cephalosporins, carbapenems, and monobactams (odds ratio [OR], 4.25; 95% confidence interval [CI], 1.74–10.4; <em>P</em> = 0.002), and an exploratory analysis suggested a dose-response per day prescribed (OR, 1.07; 95% CI, 1.03–1.11; <em>P</em> = 0.001). When restricted to BW <750 g or GA <27 weeks (N = 259, with 49 treated for ROP), these associations remained significant (OR, 3.87; 95% CI, 1.57–9.51; <em>P</em> = 0.003; per day prescribed: OR, 1.07; 95% CI, 1.03–1.11; <em>P</em> = 0.001). After propensity score matching for BW, GA, BPD, sepsis, and any bacterial infection, the average percent of infants who required treatment was 9.9 percentage points higher among those who received cephalosporins, carbapenems, and monobactams compared to those same infants if they had not received them (95% CI, 2.0–17.8 percentage points; <em>P</em> = 0.014).</div></div><div><h3>Conclusions</h3><div>Early exposure to broad-spectrum antibiotic classes, particularly cephalosporins, carbapenems, and monobactams, may be associated with type 1 ROP.</div></div><div><h3>Financial Disclosure(s)</h3><div>The authors has no/the authors have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100919"},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268155","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 : 2025-08-20DOI: 10.1016/j.xops.2025.100922
Fengbin Lin MD, PhD , Liu Li MD , Dilimulati Xiaokaiti MD , Sujie Fan MD , Zhihong Zhang MD , Yangfan Yang MD, PhD , Guangxian Tang MD, PhD , Hengli Zhang MD, PhD , Yawen Li MD , Yunhe Song MD, PhD , Zhixuan Wang MD , Zige Fang MD , Jiangang Xu MD, PhD , Xiulan Zhang MD, PhD
Purpose
To evaluate the 2-year outcomes of goniotomy (GT) in patients with prior failed glaucoma surgery.
Design
A prospective, observational multicentered study.
Participants
Patients who underwent GT after previous failed glaucoma surgery.
Methods
Patients were enrolled from May 2021 to October 2022. They underwent comprehensive ophthalmic examination, including medical history review, slit lamp examination, best-corrected visual acuity, and intraocular pressure (IOP) assessments preoperatively and postoperatively. Postoperative complications were also evaluated. Complete success was defined as IOP of 6 to 18 mmHg with ≥20% reduction from baseline, without medication. Qualified success required similar IOP control with medication.
Main Outcome Measures
Intraocular pressure change, medication use, treatment success rate, and postoperative complications over 24 months.
Results
A total of 61 eyes from 51 patients were included, with 20 eyes (17 patients) diagnosed with primary open-angle glaucoma and 41 eyes (34 patients) with primary angle-closure glaucoma as their primary condition. The mean age was 60.6 ± 10.6 years, with 30 (58.8%) female patients. Prior surgeries included peripheral iridectomy (23 eyes), trabeculectomy (39 eyes), XEN Gel implant (1 eye), Ahmed valve implant (1 eye), and phacoemulsification and intraocular lens implantation (17 eyes). Among these, complete success was achieved in 26 eyes (42.6%) and qualified success in 52 eyes (85.2%). The mean IOP dropped from 26.4 ± 6.2 mmHg preoperatively to 16.3 ± 4.8 mmHg at 24 months (35.8% reduction; P < 0.001). Antiglaucoma medications decreased from 2.6 ± 1.2 to 1.4 ± 1.4 over 24 months (P < 0.001). Best-corrected visual acuity remained stable during the follow-up (P = 0.987). Complications included hyphema (n = 7), IOP spikes (n = 6), mild corneal edema (n = 3), and shallow anterior chamber (n = 2), all within the first postoperative month. Regression analysis showed that older age was positively correlated with complete success (odds ratio = 1.06; 95% confidence interval, 1.00–1.12; P = 0.044) and qualified success (odds ratio = 1.16; 95% confidence interval, 1.05–1.28; P = 0.004). Primary open-angle glaucoma was negatively associated with qualified success (odds ratio = 0.18; 95% confidence interval, 0.04–0.84; P = 0.029).
Conclusions
Goniotomy proves to be a safe and effective procedure for patients with previous failed glaucoma surgery over the 24-month study period.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Two-Year Outcomes of Goniotomy After Failed Surgery for Glaucoma: A Multicenter Study","authors":"Fengbin Lin MD, PhD , Liu Li MD , Dilimulati Xiaokaiti MD , Sujie Fan MD , Zhihong Zhang MD , Yangfan Yang MD, PhD , Guangxian Tang MD, PhD , Hengli Zhang MD, PhD , Yawen Li MD , Yunhe Song MD, PhD , Zhixuan Wang MD , Zige Fang MD , Jiangang Xu MD, PhD , Xiulan Zhang MD, PhD","doi":"10.1016/j.xops.2025.100922","DOIUrl":"10.1016/j.xops.2025.100922","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the 2-year outcomes of goniotomy (GT) in patients with prior failed glaucoma surgery.</div></div><div><h3>Design</h3><div>A prospective, observational multicentered study.</div></div><div><h3>Participants</h3><div>Patients who underwent GT after previous failed glaucoma surgery.</div></div><div><h3>Methods</h3><div>Patients were enrolled from May 2021 to October 2022. They underwent comprehensive ophthalmic examination, including medical history review, slit lamp examination, best-corrected visual acuity, and intraocular pressure (IOP) assessments preoperatively and postoperatively. Postoperative complications were also evaluated. Complete success was defined as IOP of 6 to 18 mmHg with ≥20% reduction from baseline, without medication. Qualified success required similar IOP control with medication.</div></div><div><h3>Main Outcome Measures</h3><div>Intraocular pressure change, medication use, treatment success rate, and postoperative complications over 24 months.</div></div><div><h3>Results</h3><div>A total of 61 eyes from 51 patients were included, with 20 eyes (17 patients) diagnosed with primary open-angle glaucoma and 41 eyes (34 patients) with primary angle-closure glaucoma as their primary condition. The mean age was 60.6 ± 10.6 years, with 30 (58.8%) female patients. Prior surgeries included peripheral iridectomy (23 eyes), trabeculectomy (39 eyes), XEN Gel implant (1 eye), Ahmed valve implant (1 eye), and phacoemulsification and intraocular lens implantation (17 eyes). Among these, complete success was achieved in 26 eyes (42.6%) and qualified success in 52 eyes (85.2%). The mean IOP dropped from 26.4 ± 6.2 mmHg preoperatively to 16.3 ± 4.8 mmHg at 24 months (35.8% reduction; <em>P</em> < 0.001). Antiglaucoma medications decreased from 2.6 ± 1.2 to 1.4 ± 1.4 over 24 months (<em>P</em> < 0.001). Best-corrected visual acuity remained stable during the follow-up (<em>P</em> = 0.987). Complications included hyphema (n = 7), IOP spikes (n = 6), mild corneal edema (n = 3), and shallow anterior chamber (n = 2), all within the first postoperative month. Regression analysis showed that older age was positively correlated with complete success (odds ratio = 1.06; 95% confidence interval, 1.00–1.12; <em>P</em> = 0.044) and qualified success (odds ratio = 1.16; 95% confidence interval, 1.05–1.28; <em>P</em> = 0.004). Primary open-angle glaucoma was negatively associated with qualified success (odds ratio = 0.18; 95% confidence interval, 0.04–0.84; <em>P</em> = 0.029).</div></div><div><h3>Conclusions</h3><div>Goniotomy proves to be a safe and effective procedure for patients with previous failed glaucoma surgery over the 24-month study period.</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 100922"},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109330","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 evaluate the neuroprotective efficacy of topical WIN 55 212-2 (WIN) in the DBA/2J mouse model of chronic glaucoma.
Design
Preclinical controlled study.
Subjects
Ninety 6-month-old DBA/2J mice (180 eyes) grouped in Untreated (UN), WIN 1%, or WIN 1% + rimonabant (RIM).
Methods
In vivo recordings were performed at 6 (T6), 8 (T8), and 10 (T10) months. Two broken-stick generalized estimating equation models were fitted: model 1 treated Intraocular Pressure (IOP) as a covariate; model 2 treated IOP as an explicit predictor. Retinal lysates underwent Western blotting (LC3-II, p62, Parkin, Optineurin, RNA-binding protein with multiple splicing (RBPMS), α-spectrin breakdown products [SBDPs]), and untargeted proteomics for exploratory mechanistic granularity assessment.
Main Outcome Measures
Pattern electroretinogram (PERG), IOP, flash ERG (FERG), and photopic negative response amplitudes as well as ganglion cell complex (GCC) thickness.
Results
At T8, IOP was 11.5 ± 1.4 mmHg in WIN compared to 22.0 ± 2.0 mmHg in UN and 21.7 ± 2.3 mmHg in RIM (P < 0.001). Similar results were observed at T10 (WIN: 19.4 ± 3.0 mmHg; UN: 23.4 ± 2.0 mmHg; RIM: 22.7 ± 3.2 mmHg) (P < 0.001). Statistically significant differences in PERG amplitude were observed among groups at both T8 and T10. In model 1, WIN-treated eyes demonstrated a 6.1 μV higher PERG amplitude at T10 (P < 0.001). Model 2 showed no significant WIN×IOP×T10 interaction (P = 0.757), suggesting that WIN-mediated protection is largely independent of IOP. Time-dependent decline in FERG was similar among groups. Photopic negative response amplitudes and GCC thickness decreased in all groups, with significant intergroup differences favoring WIN at both T8 and T10 (both P < 0.001). Molecularly, WIN reduced LC3-II by 35% at T10 without p62 accumulation, doubled Parkin and lowered Optineurin at T8, and markedly blunted RBPMS downregulation and SBDP accumulation (SBDP-120 kDa: –65% at T10). Proteomics identified 15 downregulated proteins in WIN retinas associated with relief of lysosomal antiprotease and Ca2+-stress pathways and enhanced autophagy–mitophagy flux.
Conclusions
Topical WIN 1% transiently lowers IOP, preserves retinal ganglion cell function, and attenuates structural and molecular degeneration in a seemingly cannabinoid receptor 1–dependent and IOP-independent fashion, thus representing a promising neuroprotective strategy for glaucoma.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Topical WIN 55 212-2 Confers Long-Term Intraocular Pressure–Independent Neuroprotection in the DBA/2J Mouse Model of Glaucoma","authors":"Gabriele Gallo Afflitto MD , Tsung-Han Chou PhD , Mascha Louisa Korsch PhD , Francesco Aiello MD, PhD , Annagrazia Adornetto PhD , Rossella Russo PhD , Giacinto Bagetta MD , Carlo Nucci MD, PhD , Vittorio Porciatti DSc","doi":"10.1016/j.xops.2025.100918","DOIUrl":"10.1016/j.xops.2025.100918","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the neuroprotective efficacy of topical WIN 55 212-2 (WIN) in the DBA/2J mouse model of chronic glaucoma.</div></div><div><h3>Design</h3><div>Preclinical controlled study.</div></div><div><h3>Subjects</h3><div>Ninety 6-month-old DBA/2J mice (180 eyes) grouped in Untreated (UN), WIN 1%, or WIN 1% + rimonabant (RIM).</div></div><div><h3>Methods</h3><div>In vivo recordings were performed at 6 (T6), 8 (T8), and 10 (T10) months. Two broken-stick generalized estimating equation models were fitted: model 1 treated Intraocular Pressure (IOP) as a covariate; model 2 treated IOP as an explicit predictor. Retinal lysates underwent Western blotting (LC3-II, p62, Parkin, Optineurin, RNA-binding protein with multiple splicing (RBPMS), α-spectrin breakdown products [SBDPs]), and untargeted proteomics for exploratory mechanistic granularity assessment.</div></div><div><h3>Main Outcome Measures</h3><div>Pattern electroretinogram (PERG), IOP, flash ERG (FERG), and photopic negative response amplitudes as well as ganglion cell complex (GCC) thickness.</div></div><div><h3>Results</h3><div>At T8, IOP was 11.5 ± 1.4 mmHg in WIN compared to 22.0 ± 2.0 mmHg in UN and 21.7 ± 2.3 mmHg in RIM (<em>P</em> < 0.001). Similar results were observed at T10 (WIN: 19.4 ± 3.0 mmHg; UN: 23.4 ± 2.0 mmHg; RIM: 22.7 ± 3.2 mmHg) (<em>P</em> < 0.001). Statistically significant differences in PERG amplitude were observed among groups at both T8 and T10. In model 1, WIN-treated eyes demonstrated a 6.1 μV higher PERG amplitude at T10 (<em>P</em> < 0.001). Model 2 showed no significant WIN×IOP×T10 interaction (<em>P</em> = 0.757), suggesting that WIN-mediated protection is largely independent of IOP. Time-dependent decline in FERG was similar among groups. Photopic negative response amplitudes and GCC thickness decreased in all groups, with significant intergroup differences favoring WIN at both T8 and T10 (both <em>P</em> < 0.001). Molecularly, WIN reduced LC3-II by 35% at T10 without p62 accumulation, doubled Parkin and lowered Optineurin at T8, and markedly blunted RBPMS downregulation and SBDP accumulation (SBDP-120 kDa: –65% at T10). Proteomics identified 15 downregulated proteins in WIN retinas associated with relief of lysosomal antiprotease and Ca<sup>2+</sup>-stress pathways and enhanced autophagy–mitophagy flux.</div></div><div><h3>Conclusions</h3><div>Topical WIN 1% transiently lowers IOP, preserves retinal ganglion cell function, and attenuates structural and molecular degeneration in a seemingly cannabinoid receptor 1–dependent and IOP-independent fashion, thus representing a promising neuroprotective strategy for glaucoma.</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 100918"},"PeriodicalIF":4.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159827","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 : 2025-08-18DOI: 10.1016/j.xops.2025.100916
Serena Zacharias MD , Joseph Kreis , Natalie Ungaretti , Emma Warr , Heather Heitkotter PhD , Iniya Adhan MD , Ashleigh Walesa , Katherine Hemsworth , Jenna Grieshop , Joseph Carroll PhD
Purpose
To assess the relationship between foveal cone topography, foveal outer nuclear layer (ONL) thickness, foveal morphology, and foveal avascular zone (FAZ) area in individuals with normal vision.
Design
Retrospective cross-sectional study.
Participants
A total of 68 participants with normal vision were included (49 female; 19 male).
Methods
Directional OCT images were used to derive ONL thickness measurements. Images of the foveal cone mosaic were obtained using adaptive optics scanning light ophthalmoscopy, from which peak cone density (PCD) was measured. Foveal avascular zone area and foveal pit morphology were estimated using OCT angiography images and OCT macular thickness maps, respectively.
Main Outcome Measures
Foveal cone density metrics, foveal ONL thickness, foveal pit diameter and volume, and FAZ area.
Results
There was a weak positive correlation between maximum ONL thickness and PCD in individuals with normal vision (r = 0.23; P = 0.06), and PCD was significantly negatively correlated with both foveal pit diameter (r = –0.54; P < 0.0001) and foveal pit volume (r = –0.39; P = 0.0011).
Conclusions
Findings suggest that foveal ONL thickness should be used with caution as a clinical biomarker of foveal cone density, at least when measured using current OCT technology. The relationship between foveal pit size and foveal cone density supports possible mechanistic links between the processes that establish these important features of foveal specialization.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
目的探讨视力正常个体中央凹锥体形貌、中央凹外核层（ONL）厚度、中央凹形态与中央凹无血管区（FAZ）面积的关系。设计：回顾性横断面研究。参与者共纳入68名视力正常的参与者（女性49人，男性19人）。方法采用定向OCT图像进行ONL厚度测量。采用自适应光学扫描光检法获得中央凹锥体镶嵌图像，测量锥体峰值密度（PCD）。分别利用OCT血管造影图像和OCT黄斑厚度图估计中央凹无血管区面积和中央凹凹形态。主要观察指标：中央凹锥体密度指标、中央凹ONL厚度、中央凹凹直径和体积、FAZ面积。结果视力正常者最大ONL厚度与PCD呈弱正相关（r = 0.23; P = 0.06）， PCD与中央凹窝直径（r = -0.54; P < 0.0001）和中央凹窝体积（r = -0.39; P = 0.0011）呈显著负相关。结论研究结果表明，至少在使用当前OCT技术测量时，应谨慎使用中央凹ONL厚度作为中央凹锥体密度的临床生物标志物。中央凹凹大小和中央凹锥密度之间的关系支持了建立中央凹特化这些重要特征的过程之间可能的机制联系。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":"Assessing the Relationship between Foveal Cone Density, Outer Nuclear Layer Thickness and Foveal Morphology","authors":"Serena Zacharias MD , Joseph Kreis , Natalie Ungaretti , Emma Warr , Heather Heitkotter PhD , Iniya Adhan MD , Ashleigh Walesa , Katherine Hemsworth , Jenna Grieshop , Joseph Carroll PhD","doi":"10.1016/j.xops.2025.100916","DOIUrl":"10.1016/j.xops.2025.100916","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the relationship between foveal cone topography, foveal outer nuclear layer (ONL) thickness, foveal morphology, and foveal avascular zone (FAZ) area in individuals with normal vision.</div></div><div><h3>Design</h3><div>Retrospective cross-sectional study.</div></div><div><h3>Participants</h3><div>A total of 68 participants with normal vision were included (49 female; 19 male).</div></div><div><h3>Methods</h3><div>Directional OCT images were used to derive ONL thickness measurements. Images of the foveal cone mosaic were obtained using adaptive optics scanning light ophthalmoscopy, from which peak cone density (PCD) was measured. Foveal avascular zone area and foveal pit morphology were estimated using OCT angiography images and OCT macular thickness maps, respectively.</div></div><div><h3>Main Outcome Measures</h3><div>Foveal cone density metrics, foveal ONL thickness, foveal pit diameter and volume, and FAZ area.</div></div><div><h3>Results</h3><div>There was a weak positive correlation between maximum ONL thickness and PCD in individuals with normal vision (r = 0.23; <em>P</em> = 0.06), and PCD was significantly negatively correlated with both foveal pit diameter (r = –0.54; <em>P</em> < 0.0001) and foveal pit volume (r = –0.39; <em>P</em> = 0.0011).</div></div><div><h3>Conclusions</h3><div>Findings suggest that foveal ONL thickness should be used with caution as a clinical biomarker of foveal cone density, at least when measured using current OCT technology. The relationship between foveal pit size and foveal cone density supports possible mechanistic links between the processes that establish these important features of foveal specialization.</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 100916"},"PeriodicalIF":4.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159826","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 : 2025-08-18DOI: 10.1016/j.xops.2025.100917
Sarah Aman MBBS , Melat Asebot MD, MPH , Dhruva Patel BS , Elizabeth A. Brown MPH , Ana Collazo Martinez MPH , Edward Kuwera MD , Viet-Hoan Le PhD , Yi Zhang MS , Ruikang K. Wang PhD , Risa M. Wolf MD , Amir H. Kashani MD, PhD
Objective
To evaluate chorioretinal microvasculature using OCT angiography (OCTA) in children with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) without diabetic retinopathy (DR), compared with healthy controls.
Design
A cross-sectional, observational study.
Participants
Subjects with T1DM and T2DM without DR were recruited from the pediatric diabetes center, and nondiabetic controls were recruited from the pediatric eye clinic from 2022 to 2024.
Methods
All participants underwent color fundus and 1050 nm swept-source OCTA imaging (3 × 3, 6 × 6, and 12 × 12 mm2). Quantitative OCTA analyses were performed using a custom MATLAB algorithm. Retinal segmentation was performed for the superficial retinal layer, the deep retinal layer, the whole retina, and the choroid. A linear mixed effects regression model was used to compare the results between youth with diabetes and controls, adjusting for age.
Main Outcome Measures
Mean values for retinal thickness, vessel skeleton density (VSD), vessel diameter index (VDI), mean choroidal thickness (MCT), choroidal vascularity index (CVI), choroidal vascular volume (CVV), and choriocapillaris thickness.
Results
A total of 32 subjects (44% females, 57 eyes) were included as follows: 10 T1DM, 7 T2DM, and 15 without diabetes. For youth with T1DM, age was 16 ± 2 years, glycated hemoglobin was 7.7 ± 0.9%, and diabetes mellitus (DM) duration was 8.0 ± 4 years. For youth with T2DM, age was 16 ± 2 years, mean glycated hemoglobin was 8.7 ± 3.5%, and mean DM duration was 2.4 ± 1.3 years. Age for youth without diabetes was 12 ± 5 years. Choroidal vascularity index and CVV were significantly higher in T1DM compared with controls (CVI: 0.69 ± 0.04 vs. 0.63 ± 0.05, P = 0.001; CVV: 18.9 ± 5.0 vs. 16.2 ± 2.0 mm3, P = 0.001) but not in T2DM. Choriocapillaris thickness was also significantly higher in T1DM (9.5 ± 1.2 μm) compared with controls (8.4 ± 1.0 μm, P = 0.003), with no significant difference in T2DM. Retinal thickness, MCT, VSD, VDI, and flux were not different among groups (P > 0.05).
Conclusions
Children with T1DM without DR exhibited larger choroidal and choriocapillaris vascularity than controls and no contemporaneous differences in retinal vascularity measures. This suggests that subclinical choroidal changes are present in pediatric diabetic patients before clinical or subclinical signs of DR.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"OCT Angiography of Chorioretinal Microvasculature in Children with Type 1 and Type 2 Diabetes without Retinopathy","authors":"Sarah Aman MBBS , Melat Asebot MD, MPH , Dhruva Patel BS , Elizabeth A. Brown MPH , Ana Collazo Martinez MPH , Edward Kuwera MD , Viet-Hoan Le PhD , Yi Zhang MS , Ruikang K. Wang PhD , Risa M. Wolf MD , Amir H. Kashani MD, PhD","doi":"10.1016/j.xops.2025.100917","DOIUrl":"10.1016/j.xops.2025.100917","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate chorioretinal microvasculature using OCT angiography (OCTA) in children with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) without diabetic retinopathy (DR), compared with healthy controls.</div></div><div><h3>Design</h3><div>A cross-sectional, observational study.</div></div><div><h3>Participants</h3><div>Subjects with T1DM and T2DM without DR were recruited from the pediatric diabetes center, and nondiabetic controls were recruited from the pediatric eye clinic from 2022 to 2024.</div></div><div><h3>Methods</h3><div>All participants underwent color fundus and 1050 nm swept-source OCTA imaging (3 × 3, 6 × 6, and 12 × 12 mm<sup>2</sup>). Quantitative OCTA analyses were performed using a custom MATLAB algorithm. Retinal segmentation was performed for the superficial retinal layer, the deep retinal layer, the whole retina, and the choroid. A linear mixed effects regression model was used to compare the results between youth with diabetes and controls, adjusting for age.</div></div><div><h3>Main Outcome Measures</h3><div>Mean values for retinal thickness, vessel skeleton density (VSD), vessel diameter index (VDI), mean choroidal thickness (MCT), choroidal vascularity index (CVI), choroidal vascular volume (CVV), and choriocapillaris thickness.</div></div><div><h3>Results</h3><div>A total of 32 subjects (44% females, 57 eyes) were included as follows: 10 T1DM, 7 T2DM, and 15 without diabetes. For youth with T1DM, age was 16 ± 2 years, glycated hemoglobin was 7.7 ± 0.9%, and diabetes mellitus (DM) duration was 8.0 ± 4 years. For youth with T2DM, age was 16 ± 2 years, mean glycated hemoglobin was 8.7 ± 3.5%, and mean DM duration was 2.4 ± 1.3 years. Age for youth without diabetes was 12 ± 5 years. Choroidal vascularity index and CVV were significantly higher in T1DM compared with controls (CVI: 0.69 ± 0.04 vs. 0.63 ± 0.05, <em>P</em> = 0.001; CVV: 18.9 ± 5.0 vs. 16.2 ± 2.0 mm<sup>3</sup>, <em>P</em> = 0.001) but not in T2DM. Choriocapillaris thickness was also significantly higher in T1DM (9.5 ± 1.2 μm) compared with controls (8.4 ± 1.0 μm, <em>P</em> = 0.003), with no significant difference in T2DM. Retinal thickness, MCT, VSD, VDI, and flux were not different among groups (<em>P</em> > 0.05).</div></div><div><h3>Conclusions</h3><div>Children with T1DM without DR exhibited larger choroidal and choriocapillaris vascularity than controls and no contemporaneous differences in retinal vascularity measures. This suggests that subclinical choroidal changes are present in pediatric diabetic patients before clinical or subclinical signs of 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 100917"},"PeriodicalIF":4.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121159","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 : 2025-08-14DOI: 10.1016/j.xops.2025.100913
Tong Li MD, PhD , Shiqi Yang MD, PhD , Qinghuai Liu MD , Yanping Song MS , Jianping Tong MD , Wenbin Wei MD , Weiqi Chen BS , Hong Dai MD , Wei Wang MS , Miaoqin Wu MD , Guohong Zhou MD , Xuan Xiao MD , Jinglin Zhang MD , Rongrong Zhu MS , Haoyu Li MS , Yafang Wang PhD , Xiaoyu Chen PhD , Shujie Lu MS , Haiwei Du PhD , Han Han-Zhang PhD , Xiaodong Sun MD, PhD
Purpose
This study aims to evaluate the efficacy and safety of high-dose efdamrofusp alfa (IBI302, targeting VEGF and complement C3b/4b) with personalized dosing intervals in patients with neovascular age-related macular degeneration (nAMD).
Design
A multicenter, randomized, double-masked, active-controlled, noninferiority phase II trial.
Participants
A total of 132 anti-VEGF naïve or previously treated participants with nAMD were enrolled.
Methods
Eligible participants were randomized (1:1:1) to receive IBI302 6.4 mg, IBI302 8.0 mg, or aflibercept 2.0 mg. Efdamrofusp alfa groups were dosed every 8 weeks (Q8W) or every 12 weeks (Q12W), based on disease activity assessment at week 20, after 4 monthly injections. The aflibercept 2.0-mg group was dosed Q8W, after 3 monthly injections.
Main Outcome Measures
The primary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to week 40. The prespecified noninferiority margin was 4 letters.
Results
The least squares mean (standard error) changes in BCVA from baseline to week 40 were +10.5 (1.5) letters with IBI302 6.4 mg, +9.2 (1.5) letters with IBI302 8.0 mg, and +9.7 (1.5) letters with aflibercept 2.0 mg. The estimated differences were +0.8 (80% confidence interval: –1.9 to 3.6, noninferiority test: P = 0.0115) for IBI302 6.4 mg versus aflibercept 2.0 mg and –0.5 (–3.3 to 2.2, noninferiority test: P = 0.0123) for IBI302 8.0 mg versus aflibercept 2.0 mg. Over 80% of participants in IBI302 groups were dosed Q12W after week 20 and maintained their regimens until the end of study. Treatment-emergent adverse events (TEAEs) in the study eye were reported in 36.4% of participants receiving IBI302 6.4 mg, 37.8% receiving IBI302 8.0 mg, and 23.3% receiving aflibercept 2.0 mg. The most common ocular TEAE was conjunctival hemorrhage (9.1% for 6.4 mg and 11.1% for 8.0 mg) in both IBI302 groups, whereas cataract (7.0%) was the most frequent ocular TEAE in the aflibercept 2.0-mg group.
Conclusions
Efdamrofusp alfa 6.4 and 8.0 mg dosed up to Q12W demonstrated noninferior visual gain to aflibercept 2.0 mg Q8W. Moreover, IBI302 groups were well tolerated. These findings suggested that high-dose IBI302 with extended dosing intervals could provide sustained visual benefits for patients with nAMD.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Efficacy and Safety of Efdamrofusp Alfa with Personalized Dosing Intervals in Neovascular Age-Related Macular Degeneration: A Phase II Trial","authors":"Tong Li MD, PhD , Shiqi Yang MD, PhD , Qinghuai Liu MD , Yanping Song MS , Jianping Tong MD , Wenbin Wei MD , Weiqi Chen BS , Hong Dai MD , Wei Wang MS , Miaoqin Wu MD , Guohong Zhou MD , Xuan Xiao MD , Jinglin Zhang MD , Rongrong Zhu MS , Haoyu Li MS , Yafang Wang PhD , Xiaoyu Chen PhD , Shujie Lu MS , Haiwei Du PhD , Han Han-Zhang PhD , Xiaodong Sun MD, PhD","doi":"10.1016/j.xops.2025.100913","DOIUrl":"10.1016/j.xops.2025.100913","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to evaluate the efficacy and safety of high-dose efdamrofusp alfa (IBI302, targeting VEGF and complement C3b/4b) with personalized dosing intervals in patients with neovascular age-related macular degeneration (nAMD).</div></div><div><h3>Design</h3><div>A multicenter, randomized, double-masked, active-controlled, noninferiority phase II trial.</div></div><div><h3>Participants</h3><div>A total of 132 anti-VEGF naïve or previously treated participants with nAMD were enrolled.</div></div><div><h3>Methods</h3><div>Eligible participants were randomized (1:1:1) to receive IBI302 6.4 mg, IBI302 8.0 mg, or aflibercept 2.0 mg. Efdamrofusp alfa groups were dosed every 8 weeks (Q8W) or every 12 weeks (Q12W), based on disease activity assessment at week 20, after 4 monthly injections. The aflibercept 2.0-mg group was dosed Q8W, after 3 monthly injections.</div></div><div><h3>Main Outcome Measures</h3><div>The primary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to week 40. The prespecified noninferiority margin was 4 letters.</div></div><div><h3>Results</h3><div>The least squares mean (standard error) changes in BCVA from baseline to week 40 were +10.5 (1.5) letters with IBI302 6.4 mg, +9.2 (1.5) letters with IBI302 8.0 mg, and +9.7 (1.5) letters with aflibercept 2.0 mg. The estimated differences were +0.8 (80% confidence interval: –1.9 to 3.6, noninferiority test: P = 0.0115) for IBI302 6.4 mg versus aflibercept 2.0 mg and –0.5 (–3.3 to 2.2, noninferiority test: P = 0.0123) for IBI302 8.0 mg versus aflibercept 2.0 mg. Over 80% of participants in IBI302 groups were dosed Q12W after week 20 and maintained their regimens until the end of study. Treatment-emergent adverse events (TEAEs) in the study eye were reported in 36.4% of participants receiving IBI302 6.4 mg, 37.8% receiving IBI302 8.0 mg, and 23.3% receiving aflibercept 2.0 mg. The most common ocular TEAE was conjunctival hemorrhage (9.1% for 6.4 mg and 11.1% for 8.0 mg) in both IBI302 groups, whereas cataract (7.0%) was the most frequent ocular TEAE in the aflibercept 2.0-mg group.</div></div><div><h3>Conclusions</h3><div>Efdamrofusp alfa 6.4 and 8.0 mg dosed up to Q12W demonstrated noninferior visual gain to aflibercept 2.0 mg Q8W. Moreover, IBI302 groups were well tolerated. These findings suggested that high-dose IBI302 with extended dosing intervals could provide sustained visual benefits for patients with nAMD.</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 100913"},"PeriodicalIF":4.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109331","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 : 2025-08-14DOI: 10.1016/j.xops.2025.100915
Nuno Gouveia MD, MSc , Jessica Karuntu MD , Hind Almushattat MD , Rufino Silva MD, PhD , Camiel Boon MD, PhD , João Pedro Marques MD, PhD
Purpose
To characterize the genetic, structural, and patient-reported visual function features in a multicenter cohort of patients with retinitis pigmentosa GTPase regulator (RPGR)–associated retinal degeneration.
Design
A cross-sectional, exploratory, international, multicenter study conducted across 3 academic centers.
Subjects
The study included 102 eyes from 51 patients (37.3% female) with genetically confirmed RPGR-associated retinal degeneration. Only male and female patients with a retinitis pigmentosa (RP) phenotype were included, as well as female carriers from RP pedigrees with retinal degeneration.
Methods
Genetic variants were identified and visual acuity (VA) was recorded. Retinal phenotype was classified using fundus autofluorescence. Structural retinal features were assessed using spectral-domain OCT to measure ellipsoid zone (EZ) area and width, central subfield thickness (CST), central point thickness (CPT), subfoveal outer nuclear layer (ONL) thickness, photoreceptor outer segment length (PROS), foveal outer segment pigment epithelial thickness (FOSPET), and FOSPET-PROS ratio. Patient-reported visual function was measured via the Michigan Retinal Degeneration Questionnaire (MRDQ).
Main Outcome Measures
Associations between genetic variant location, retinal structural parameters, and VA, as well as correlations between structural measures and MRDQ domain scores.
Results
Structural endpoints, including EZ area, CPT, PROS, and FOSPET, correlated significantly with all MRDQ domains, and higher disability scores on MRDQ were associated with more advanced retinal degeneration. There were no significant differences in VA or structural features between RPGR variants located in the open reading frame 15 region compared to exons 1 to 13. Eyes from male patients and female patients with an RP phenotype showed significantly decreased VA and structural features compared with eyes of female carriers with focal or radial pattern. A mixed model analysis found that VA was associated with several OCT features including CST, CPT, ONL thickness, EZ area, PROS, and FOSPET.
Conclusions
This study underscores the value of combining genetic, structural, and patient-reported outcome measures in understanding RPGR-associated retinal degeneration. Structural biomarkers provide valuable insights into disease severity and visual impairment, aligning closely with patient-reported visual function. This approach supports further development of patient-centered outcome measures for clinical trials and therapeutic interventions.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Retinitis Pigmentosa GTPase regulator–Associated Retinal Degeneration: Integrating Patient-Reported Outcomes, Genetic, and Structural Biomarkers","authors":"Nuno Gouveia MD, MSc , Jessica Karuntu MD , Hind Almushattat MD , Rufino Silva MD, PhD , Camiel Boon MD, PhD , João Pedro Marques MD, PhD","doi":"10.1016/j.xops.2025.100915","DOIUrl":"10.1016/j.xops.2025.100915","url":null,"abstract":"<div><h3>Purpose</h3><div>To characterize the genetic, structural, and patient-reported visual function features in a multicenter cohort of patients with retinitis pigmentosa GTPase regulator (<em>RPGR</em>)–associated retinal degeneration.</div></div><div><h3>Design</h3><div>A cross-sectional, exploratory, international, multicenter study conducted across 3 academic centers.</div></div><div><h3>Subjects</h3><div>The study included 102 eyes from 51 patients (37.3% female) with genetically confirmed <em>RPGR</em>-associated retinal degeneration. Only male and female patients with a retinitis pigmentosa (RP) phenotype were included, as well as female carriers from RP pedigrees with retinal degeneration.</div></div><div><h3>Methods</h3><div>Genetic variants were identified and visual acuity (VA) was recorded. Retinal phenotype was classified using fundus autofluorescence. Structural retinal features were assessed using spectral-domain OCT to measure ellipsoid zone (EZ) area and width, central subfield thickness (CST), central point thickness (CPT), subfoveal outer nuclear layer (ONL) thickness, photoreceptor outer segment length (PROS), foveal outer segment pigment epithelial thickness (FOSPET), and FOSPET-PROS ratio. Patient-reported visual function was measured via the Michigan Retinal Degeneration Questionnaire (MRDQ).</div></div><div><h3>Main Outcome Measures</h3><div>Associations between genetic variant location, retinal structural parameters, and VA, as well as correlations between structural measures and MRDQ domain scores.</div></div><div><h3>Results</h3><div>Structural endpoints, including EZ area, CPT, PROS, and FOSPET, correlated significantly with all MRDQ domains, and higher disability scores on MRDQ were associated with more advanced retinal degeneration. There were no significant differences in VA or structural features between <em>RPGR</em> variants located in the open reading frame 15 region compared to exons 1 to 13. Eyes from male patients and female patients with an RP phenotype showed significantly decreased VA and structural features compared with eyes of female carriers with focal or radial pattern. A mixed model analysis found that VA was associated with several OCT features including CST, CPT, ONL thickness, EZ area, PROS, and FOSPET.</div></div><div><h3>Conclusions</h3><div>This study underscores the value of combining genetic, structural, and patient-reported outcome measures in understanding <em>RPGR</em>-associated retinal degeneration. Structural biomarkers provide valuable insights into disease severity and visual impairment, aligning closely with patient-reported visual function. This approach supports further development of patient-centered outcome measures for clinical trials and therapeutic interventions.</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 100915"},"PeriodicalIF":4.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109420","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 : 2025-08-14DOI: 10.1016/j.xops.2025.100914
Kai Yuan Tey MBBS , Brian Juin Hsein Lee MBBS , Clarissa Ng MBBS , Qiu Ying Wong , Satish K. Panda PhD , Amrit Dash , Jipson Wong , Ezekiel Ze Ken Cheong MD , Jodhbir S. Mehta FRCS(Ed), PhD , Leopold Schmeterer MSc, PhD , Khin Yadanar Win PhD , Damon Wong PhD , Marcus Ang FRCS(Ed), PhD
Purpose
To evaluate the use of a deep learning network (DLN) in analyzing widefield specular microscopy (WFSM) images in eyes with Fuchs endothelial corneal dystrophy (FECD).
Design
Cross-sectional clinical observational study.
Participants
A total of 1839 images were obtained via WFSM imaging (CEM-530, Nidek Co Ltd) performed on 155 FECD eyes. A separate data set comprising images from 50 FECD eyes and 50 control eyes (70% training, 30% validation) was used for DLN training, which was tested on 354 images from 55 eyes from varying regions (central, paracentral, and peripheral).
Methods
Images were graded based on a standardized quality score. Central images were compared with paracentral and peripheral images in terms of quality and morphometric parameters: endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX). A U-Net-based DLN was developed and trained using the separate data set and then tested on an external longitudinal data set (baseline and 1 month). Segmentation accuracy between DLN and manual analysis was compared using the Sørensen–Dice coefficient. Morphometric outcomes (ECD, HEX, and CV) were analyzed using paired t tests.
Main Outcome Measures
Intergrader agreement for image quality and FECD severity; comparison of DLN-derived ECD with manual analysis.
Results
Strong intergrader agreement was observed for both image quality (κ = 0.967, 95% confidence interval [CI]: 0.959–0.976) and FECD severity (κ = 0.891, 95% CI: 0.786–0.995). Endothelial cell density differences between paracentral/peripheral regions were significant in eyes without or with subclinical edema (P = 0.001–0.011). Deep learning network-based segmentation closely matched manual results (Dice coefficient = 0.86 ± 0.04). Central ECD values obtained via DLN were significantly higher than manual analysis (DLN: 2633.12 ± 1167.3 cells/mm2 vs. manual: 1728.58 ± 805.69 cells/mm2, P < 0.001).
Conclusions
This study presents a novel application of deep learning for analyzing widefield corneal endothelial images. The integration of a progression visualization tool enhances interpretability, allowing efficient autoanalysis and organization of large WFSM data sets—streamlining workflows and addressing limitations of manual interpretation.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any materials discussed in this article.
{"title":"Deep Learning Analysis of Widefield Cornea Endothelial Imaging in Fuchs Dystrophy","authors":"Kai Yuan Tey MBBS , Brian Juin Hsein Lee MBBS , Clarissa Ng MBBS , Qiu Ying Wong , Satish K. Panda PhD , Amrit Dash , Jipson Wong , Ezekiel Ze Ken Cheong MD , Jodhbir S. Mehta FRCS(Ed), PhD , Leopold Schmeterer MSc, PhD , Khin Yadanar Win PhD , Damon Wong PhD , Marcus Ang FRCS(Ed), PhD","doi":"10.1016/j.xops.2025.100914","DOIUrl":"10.1016/j.xops.2025.100914","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the use of a deep learning network (DLN) in analyzing widefield specular microscopy (WFSM) images in eyes with Fuchs endothelial corneal dystrophy (FECD).</div></div><div><h3>Design</h3><div>Cross-sectional clinical observational study.</div></div><div><h3>Participants</h3><div>A total of 1839 images were obtained via WFSM imaging (CEM-530, Nidek Co Ltd) performed on 155 FECD eyes. A separate data set comprising images from 50 FECD eyes and 50 control eyes (70% training, 30% validation) was used for DLN training, which was tested on 354 images from 55 eyes from varying regions (central, paracentral, and peripheral).</div></div><div><h3>Methods</h3><div>Images were graded based on a standardized quality score. Central images were compared with paracentral and peripheral images in terms of quality and morphometric parameters: endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX). A U-Net-based DLN was developed and trained using the separate data set and then tested on an external longitudinal data set (baseline and 1 month). Segmentation accuracy between DLN and manual analysis was compared using the Sørensen–Dice coefficient. Morphometric outcomes (ECD, HEX, and CV) were analyzed using paired <em>t</em> tests.</div></div><div><h3>Main Outcome Measures</h3><div>Intergrader agreement for image quality and FECD severity; comparison of DLN-derived ECD with manual analysis.</div></div><div><h3>Results</h3><div>Strong intergrader agreement was observed for both image quality (κ = 0.967, 95% confidence interval [CI]: 0.959–0.976) and FECD severity (κ = 0.891, 95% CI: 0.786–0.995). Endothelial cell density differences between paracentral/peripheral regions were significant in eyes without or with subclinical edema (<em>P</em> = 0.001–0.011). Deep learning network-based segmentation closely matched manual results (Dice coefficient = 0.86 ± 0.04). Central ECD values obtained via DLN were significantly higher than manual analysis (DLN: 2633.12 ± 1167.3 cells/mm<sup>2</sup> vs. manual: 1728.58 ± 805.69 cells/mm<sup>2</sup>, <em>P</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>This study presents a novel application of deep learning for analyzing widefield corneal endothelial images. The integration of a progression visualization tool enhances interpretability, allowing efficient autoanalysis and organization of large WFSM data sets—streamlining workflows and addressing limitations of manual interpretation.</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 100914"},"PeriodicalIF":4.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159815","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 : 2025-08-13DOI: 10.1016/j.xops.2025.100912
David A. Sutter , Mani K. Woodward , John Jackson MD , Yakub Bayhaqi PhD , Aaron S. Coyner PhD , Shuibin Ni PhD , Susan Ostmo MS , Talita T. Lima MD , Aaron Nagiel MD, PhD , Michael F. Chiang MD, MS , Benjamin K. Young MD, MS , Yifan Jian PhD , John Peter Campbell MD, MPH
Purpose
To provide a quantitative approach to the measurement of zone in retinopathy of prematurity (ROP) using ultra-widefield OCT (UWF-OCT).
Design
Diagnostic accuracy study.
Subjects
Infants undergoing ROP screening at Oregon Health Science University between June 2023 and October 2024, whose parents consented for research imaging.
Methods
An investigational UWF-OCT captured scans from the first week of examination in which stage 1 or worse disease was noted on en face imaging in zone I, posterior zone II, or zone II, and image quality was adequate for quantitative analysis. A U-Net automatedly segmented B-scans to isolate the retina and choroid. En face images and retinal depth maps were used to manually identify the position of the optic nerve, fovea, and visualized temporal vascular border. Mean and minimum retinal arclength (RAL) was measured as the geodesic distance from the optic nerve to the vascular border. The area of vascularized retina (AVR) was estimated using the spherical cap formula, mean-RAL, and measured axial length.
Main Outcome Measures
Analysis of variance and generalized estimating equations to compare OCT-derived eye-level measurements with demographics and clinical diagnosis of zone as determined by clinical assessment of en face UWF-OCT images. Area under the receiver operating characteristic curve (AUROC) for RAL compared with zone and all biomarkers at first examination as predictors of future treatment.
Results
Eighty-five eyes from 52 patients met inclusion criteria. Retinal arclength and AVR were both associated with clinical diagnosis of zone and ranged from 7.2 to 17.3 mm and 40.3 to 213.1 mm2, respectively (P < 0.001 for both). The mean difference between zone I and zone II of 4.5 mm (95% confidence interval [CI]: 4.0–5.1) for mean-RAL (P < 0.001) and 80.9 mm2 (95% CI: 71.6–90.2) for AVR (P < 0.001). Posterior zone II was intermediate for all measurements. All measures of length and area had an AUROC >0.97 for diagnosis of zone I ROP.
Conclusions
We present a framework for objective measurement of zone in ROP using UWF-OCT. This work complements prior work leveraging advances in imaging technology to bring quantitative and objective approaches to the diagnosis and classification of ROP.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"OCT-Derived Quantitative Measurement of Extent of Vascularization (“Zone”) in Retinopathy of Prematurity","authors":"David A. Sutter , Mani K. Woodward , John Jackson MD , Yakub Bayhaqi PhD , Aaron S. Coyner PhD , Shuibin Ni PhD , Susan Ostmo MS , Talita T. Lima MD , Aaron Nagiel MD, PhD , Michael F. Chiang MD, MS , Benjamin K. Young MD, MS , Yifan Jian PhD , John Peter Campbell MD, MPH","doi":"10.1016/j.xops.2025.100912","DOIUrl":"10.1016/j.xops.2025.100912","url":null,"abstract":"<div><h3>Purpose</h3><div>To provide a quantitative approach to the measurement of zone in retinopathy of prematurity (ROP) using ultra-widefield OCT (UWF-OCT).</div></div><div><h3>Design</h3><div>Diagnostic accuracy study.</div></div><div><h3>Subjects</h3><div>Infants undergoing ROP screening at Oregon Health Science University between June 2023 and October 2024, whose parents consented for research imaging.</div></div><div><h3>Methods</h3><div>An investigational UWF-OCT captured scans from the first week of examination in which stage 1 or worse disease was noted on en face imaging in zone I, posterior zone II, or zone II, and image quality was adequate for quantitative analysis. A U-Net automatedly segmented B-scans to isolate the retina and choroid. En face images and retinal depth maps were used to manually identify the position of the optic nerve, fovea, and visualized temporal vascular border. Mean and minimum retinal arclength (RAL) was measured as the geodesic distance from the optic nerve to the vascular border. The area of vascularized retina (AVR) was estimated using the spherical cap formula, mean-RAL, and measured axial length.</div></div><div><h3>Main Outcome Measures</h3><div>Analysis of variance and generalized estimating equations to compare OCT-derived eye-level measurements with demographics and clinical diagnosis of zone as determined by clinical assessment of en face UWF-OCT images. Area under the receiver operating characteristic curve (AUROC) for RAL compared with zone and all biomarkers at first examination as predictors of future treatment.</div></div><div><h3>Results</h3><div>Eighty-five eyes from 52 patients met inclusion criteria. Retinal arclength and AVR were both associated with clinical diagnosis of zone and ranged from 7.2 to 17.3 mm and 40.3 to 213.1 mm<sup>2</sup>, respectively (<em>P</em> < 0.001 for both). The mean difference between zone I and zone II of 4.5 mm (95% confidence interval [CI]: 4.0–5.1) for mean-RAL (<em>P</em> < 0.001) and 80.9 mm<sup>2</sup> (95% CI: 71.6–90.2) for AVR (<em>P</em> < 0.001). Posterior zone II was intermediate for all measurements. All measures of length and area had an AUROC >0.97 for diagnosis of zone I ROP.</div></div><div><h3>Conclusions</h3><div>We present a framework for objective measurement of zone in ROP using UWF-OCT. This work complements prior work leveraging advances in imaging technology to bring quantitative and objective approaches to the diagnosis and classification of ROP.</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 100912"},"PeriodicalIF":4.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159828","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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