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Ten-Year Incidence, Risk Factors and Progression Rate of Macular Atrophy in Neovascular Age-Related Macular Degeneration 新生血管性年龄相关性黄斑变性患者黄斑萎缩的十年发生率、危险因素及进展率。
IF 5.6 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-09-19 DOI: 10.1111/ceo.14608
Francesco Romano, Marco Casaluci, Antonio Valastro, Matteo Airaldi, Paolo Milella, Francesco Pozzo Giuffrida, Elisa Cozzi, Andrea Aretti, Kelvin YC Teo, Chui Ming Gemmy Cheung, Marco Nassisi, Francesco Viola, Giovanni Staurenghi, Alessandro Invernizzi

Background

To evaluate the 10-year cumulative incidence, progression rates, and risk factors for macular atrophy (MA) in neovascular age-related macular degeneration (nAMD) patients receiving long-term anti-vascular endothelial growth factor (VEGF) therapy.

Methods

Retrospective, multicenter, cohort study including 148 eyes from 140 nAMD patients treated with a pro-re-nata (PRN) anti-VEGF regimen and followed for ≥ 10 years. Annual multimodal imaging—including blue autofluorescence [BAF], spectral-domain optical coherence tomography [SD-OCT] and near-infrared reflectance—was reviewed to detect and quantify MA using RegionFinder. Kaplan–Meier analysis estimated cumulative MA incidence, while mixed-effects Cox and linear regressions identified risk factors and progression rates.

Results

Baseline MA prevalence was 23.0%, increasing to 64.9% at 5 years and 79.8% at 10 years. Foveal involvement occurred in 47.4% of cases. Significant predictors for MA included baseline BCVA < 20/40 (HR = 1.50, p = 0.02), greater central subfield thickness (CST) fluctuations (HR = 1.04, p = 0.01), and more frequent submacular haemorrhages (HR = 1.34, p = 0.04). Type 3 macular neovascularization was associated with fovea-involving MA (HR = 2.03, p = 0.02). Mean MA size increased from 0.34 to 2.27 mm at 10 years, progressing at 0.20 mm/year (β = 0.15, p < 0.001). Eyes with incident MA exhibited faster progression (β = 0.03, p = 0.01) and worse BCVA decline compared to those with baseline MA (−1.96 vs. −1.42 letters/year, p < 0.001).

Conclusions

nAMD patients treated with PRN anti-VEGF therapy demonstrated a high 10-year cumulative incidence of MA (79.8%), with poor baseline BCVA and CST fluctuations as key risk factors. Eyes with incident MA progressed faster and were associated with greater visual decline, suggesting a more visually impactful atrophy.

背景:评估长期接受抗血管内皮生长因子(VEGF)治疗的新生血管性年龄相关性黄斑变性(nAMD)患者10年累积发病率、进展率和黄斑萎缩(MA)的危险因素。方法:回顾性、多中心、队列研究,包括140名接受PRN抗vegf方案治疗的nAMD患者的148只眼睛,随访≥10年。回顾了使用RegionFinder检测和量化MA的年度多模态成像技术,包括蓝色自身荧光(BAF)、光谱域光学相干层析成像(SD-OCT)和近红外反射。Kaplan-Meier分析估计累积MA发病率,而混合效应Cox和线性回归确定危险因素和进展率。结果:基线MA患病率为23.0%,5年增至64.9%,10年增至79.8%。47.4%的病例发生中央凹受累。结论:接受PRN抗vegf治疗的nAMD患者10年累积MA发病率高(79.8%),基线BCVA和CST波动差是关键危险因素。发生MA的眼睛进展更快,并伴有更大的视力下降,提示更严重的视觉影响性萎缩。
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引用次数: 0
Deep Learning-Based Detection of Reticular Pseudodrusen in Age-Related Macular Degeneration 基于深度学习的老年性黄斑变性网状假性黄斑检测。
IF 5.6 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-09-08 DOI: 10.1111/ceo.14607
Himeesh Kumar, Yelena Bagdasarova, Scott Song, Doron G. Hickey, Amy C. Cohn, Mali Okada, Robert P. Finger, Jan H. Terheyden, Ruth E. Hogg, Pierre-Henry Gabrielle, Louis Arnould, Maxime Jannaud, Xavier Hadoux, Peter van Wijngaarden, Carla J. Abbott, Lauren A. B. Hodgson, Roy Schwartz, Adnan Tufail, Emily Y. Chew, Cecilia S. Lee, Erica L. Fletcher, Melanie Bahlo, Brendan R. E. Ansell, Alice Pébay, Robyn H. Guymer, Aaron Y. Lee, Zhichao Wu

Background

Reticular pseudodrusen (RPD) signify a critical phenotype driving vision loss in age-related macular degeneration (AMD). This study sought to develop and externally test a deep learning (DL) model to detect RPD on optical coherence tomography (OCT) scans with expert-level performance.

Methods

RPD were manually segmented in 9800 OCT B-scans from individuals enrolled in a multicentre randomised trial. A DL model for instance segmentation of RPD was developed and evaluated against four retinal specialists in an internal test dataset. The primary outcome was the performance of the DL model for detecting RPD in OCT volumes in five external test datasets compared to two retinal specialists.

Results

In an internal test dataset consisting of 250 OCT B-scans, the DL model produced RPD segmentations that had higher agreement with four retinal specialists (Dice similarity coefficient [DSC] = 0.76) than the agreement amongst the specialists (DSC = 0.68; p < 0.001). In the five external test datasets consisting of 1017 eyes from 812 individuals, the DL model detected RPD in OCT volumes with a similar level of performance as two retinal specialists (area under the receiver operator characteristic curve [AUC] = 0.94, 0.95 and 0.96 respectively; p ≥ 0.32).

Conclusions

We present a DL model for automatic detection of RPD with expert-level performance, which could be used to support the clinical management of AMD. This model has been made publicly available to facilitate future research to understand this critical, yet enigmatic, AMD phenotype.

背景:网状假性黄斑变性(RPD)是导致年龄相关性黄斑变性(AMD)视力丧失的关键表型。本研究旨在开发并外部测试一种深度学习(DL)模型,以检测具有专家级性能的光学相干断层扫描(OCT)扫描上的RPD。方法:在一项多中心随机试验中,对9800名个体的OCT b扫描进行RPD手工分割。开发了一个用于RPD实例分割的DL模型,并在内部测试数据集中对四名视网膜专家进行了评估。主要结果是与两名视网膜专家相比,DL模型在五个外部测试数据集中检测OCT卷中的RPD的性能。结果:在由250个OCT b扫描组成的内部测试数据集中,DL模型产生的RPD分割与四位视网膜专家(Dice相似系数[DSC] = 0.76)的一致性高于专家之间的一致性(DSC = 0.68; p)。结论:我们提出了一个具有专家水平性能的RPD自动检测DL模型,可用于支持AMD的临床管理。该模型已公开提供,以促进未来的研究,以了解这一关键的,但神秘的,AMD表型。
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引用次数: 0
Retinal Viral Gene Therapy: Impact of Route of Administration on Serious Adverse Events—A Systematic Review 视网膜病毒基因治疗:给药途径对严重不良事件的影响——一项系统综述。
IF 5.6 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-08-21 DOI: 10.1111/ceo.14593
Aubrey Berger, Ciera D. Johnson, Alan D. Marmorstein, Brittni A. Scruggs

Background

To explore the prevalence of serious adverse events (SAEs) associated with retinal viral gene therapy and to examine trends influencing SAE occurrences in human gene therapy surgeries and pre-clinical animal trials.

Methods

Literature review was performed to identify peer-reviewed human and animal studies relevant to viral gene therapy, subretinal injections, and intravitreal injections. For clinical trials and post-approval LUXTURNA studies, only those that examined SAEs were included.

Results

Of included clinical trial studies (n = 31), SAEs were recorded in 51 out of 438 eyes (11.6%) that received subretinal injections and in 11 out of 348 eyes (3.2%) that received intravitreal injections. There were fewer intravitreal-related SAEs and less vision loss compared to subretinal gene therapy. Inflammation was the predominant SAE following intravitreal injections, whereas unexplained vision loss was the most common for subretinal injections. Clinical trials utilising subretinal injections met primary or secondary efficacy endpoints more than intravitreal trials. Eighteen studies (429 eyes) of post-approval LUXTURNA were reviewed, and SAEs were reported in 24.7% of eyes, retinal degeneration being most common (20.7%). For 58 animal studies, SAEs were recorded in 17.3% of eyes that received subretinal injections and 8.7% of eyes that received intravitreal injections.

Conclusions

Subretinal injections show higher efficacy than intravitreal injections but are associated with more serious adverse events. Consistent adverse event patterns in humans and large animals highlight their predictive value for safety. There is a need for optimised delivery methods, refined dosing protocols, and improved post-treatment monitoring to improve safety and effectiveness in gene therapy.

背景:探讨与视网膜病毒基因治疗相关的严重不良事件(SAEs)的发生率,并研究影响人类基因治疗手术和临床前动物试验中严重不良事件发生的趋势。方法:进行文献综述,以确定与病毒基因治疗、视网膜下注射和玻璃体内注射相关的同行评审的人类和动物研究。对于临床试验和批准后的LUXTURNA研究,仅包括那些检查sae的研究。结果:在纳入的临床试验研究(n = 31)中,接受视网膜下注射的438只眼中有51只(11.6%)发生了SAEs,接受玻璃体内注射的348只眼中有11只(3.2%)发生了SAEs。与视网膜下基因治疗相比,玻璃体内相关的SAEs更少,视力下降更少。炎症是玻璃体内注射后主要的SAE,而不明原因的视力丧失是视网膜下注射最常见的。使用视网膜下注射的临床试验比玻璃体内试验更能达到主要或次要疗效终点。LUXTURNA获批后的18项研究(429只眼睛)进行了回顾,24.7%的眼睛报告了SAEs,其中视网膜变性最常见(20.7%)。在58项动物研究中,17.3%接受视网膜下注射的眼睛和8.7%接受玻璃体内注射的眼睛记录了SAEs。结论:视网膜下注射比玻璃体内注射更有效,但与更严重的不良事件相关。在人类和大型动物中一致的不良事件模式突出了它们对安全性的预测价值。需要优化给药方法、改进给药方案和改进治疗后监测,以提高基因治疗的安全性和有效性。
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引用次数: 0
Continuing Professional Development 持续专业发展
IF 5.6 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-08-06 DOI: 10.1111/ceo.14581
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引用次数: 0
In the Race Against Time to Treat Vogt–Koyanagi–Harada Disease 与时间赛跑治疗Vogt-Koyanagi-Harada病
IF 5.6 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-08-06 DOI: 10.1111/ceo.14584
Judy L. Chen, Edmund Tsui
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引用次数: 0
Natural History and Biomarker Challenges in Dominant Optic Atrophy: Implications for Therapeutic Studies 显性视神经萎缩的自然历史和生物标志物挑战:对治疗研究的启示
IF 5.6 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-08-06 DOI: 10.1111/ceo.14583
Joshua Paul Harvey, Eun Hee Hong, Patrick Yu-Wai-Man
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引用次数: 0
Investigating Microinvasive Intra-Ocular Biopsy 微创眼内活检的研究。
IF 5.6 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-08-04 DOI: 10.1111/ceo.14591
Jared Ching, Shohei Kitahata, Hinako Ichikawa, Kazuaki Kadonosono

Background

Current minimally invasive methods of intraocular biopsy are confined to small gauge (G) needles and subretinal cannulae that can be prone to wound leakage at the biopsy site. We investigate the role of microneedles with internal diameters as small as 49G for intraocular biopsy in the posterior and anterior segments.

Methods

Human uveal melanoma (UM 92–1) and retinoblastoma (Y79) cancer cell lines were aspirated using microneedles of different sizes with a vitrectomy set up, and cell viability was analysed. Suspensions of cancer cells with fluorescent microbeads were injected into the subretinal space of fresh ex vivo porcine eyes before simulating biopsy with microneedle retinal puncture, followed by imaging with optical coherence tomography (OCT) and histology. Anterior chamber puncture was performed with microneedles and imaged with anterior segment OCT and examined for aqueous leakage.

Results

We find that microneedles can aspirate ocular cancer cells, both retinoblastoma and uveal melanoma, in vitro and retain a high level of cell viability, 72.83% (49G) compared to 97.00% (25G vitrector) in UM 92–1. Using an ex vivo porcine model, we find that a 49G microneedle creates a self-sealing retinal wound that does not reflux microbeads of 200 nm in diameter. Further, we find that anterior chamber puncture with a microneedle via a corneal paracentesis results in no evidence of an aqueous leak (0%) compared to a leakage rate of 100% and 66% when using a 30G and 34G needle, respectively.

Conclusion

A microinvasive approach to biopsy intraocular specimens is feasible, warranting further in vivo studies.

背景:目前的微创眼内活检方法仅限于小直径(G)针和视网膜下套管,这可能容易导致活检部位的伤口渗漏。我们研究了内径小至49G的微针在眼后和眼前段的眼内活检中的作用。方法:采用玻璃体切割装置,用不同大小的微针抽吸人葡萄膜黑色素瘤(um92 -1)和视网膜母细胞瘤(Y79)癌细胞系,分析细胞活力。将带有荧光微珠的癌细胞悬浮液注入新鲜离体猪眼视网膜下间隙,然后用微针视网膜穿刺模拟活检,然后进行光学相干断层扫描(OCT)成像和组织学检查。用微针穿刺前房,用前段OCT成像,检查房水渗漏。结果:我们发现微针可以在体外吸出眼癌细胞,包括视网膜母细胞瘤和葡萄膜黑色素瘤,并保持高水平的细胞活力,在UM 92-1中,72.83% (49G)的细胞活力高于97.00% (25G)的细胞活力。在离体猪模型中,我们发现49G微针可以产生一个自密封的视网膜伤口,该伤口不会回流直径为200nm的微珠。此外,我们发现,与使用30G和34G针的渗漏率分别为100%和66%相比,使用微针通过角膜穿刺术的前房穿刺没有水泄漏的证据(0%)。结论:微创方法对眼内标本进行活检是可行的,需要进一步的体内研究。
{"title":"Investigating Microinvasive Intra-Ocular Biopsy","authors":"Jared Ching,&nbsp;Shohei Kitahata,&nbsp;Hinako Ichikawa,&nbsp;Kazuaki Kadonosono","doi":"10.1111/ceo.14591","DOIUrl":"10.1111/ceo.14591","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Current minimally invasive methods of intraocular biopsy are confined to small gauge (G) needles and subretinal cannulae that can be prone to wound leakage at the biopsy site. We investigate the role of microneedles with internal diameters as small as 49G for intraocular biopsy in the posterior and anterior segments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human uveal melanoma (UM 92–1) and retinoblastoma (Y79) cancer cell lines were aspirated using microneedles of different sizes with a vitrectomy set up, and cell viability was analysed. Suspensions of cancer cells with fluorescent microbeads were injected into the subretinal space of fresh ex vivo porcine eyes before simulating biopsy with microneedle retinal puncture, followed by imaging with optical coherence tomography (OCT) and histology. Anterior chamber puncture was performed with microneedles and imaged with anterior segment OCT and examined for aqueous leakage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We find that microneedles can aspirate ocular cancer cells, both retinoblastoma and uveal melanoma, in vitro and retain a high level of cell viability, 72.83% (49G) compared to 97.00% (25G vitrector) in UM 92–1. Using an ex vivo porcine model, we find that a 49G microneedle creates a self-sealing retinal wound that does not reflux microbeads of 200 nm in diameter. Further, we find that anterior chamber puncture with a microneedle via a corneal paracentesis results in no evidence of an aqueous leak (0%) compared to a leakage rate of 100% and 66% when using a 30G and 34G needle, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A microinvasive approach to biopsy intraocular specimens is feasible, warranting further in vivo studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55253,"journal":{"name":"Clinical and Experimental Ophthalmology","volume":"53 8","pages":"996-1007"},"PeriodicalIF":5.6,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ceo.14591","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Progression of Loss of Vision From Centre-Involving Macular Atrophy in Eyes Treated for nAMD 在nAMD治疗的眼睛中从中心到黄斑萎缩的视力丧失的进展。
IF 5.6 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-08-03 DOI: 10.1111/ceo.14587
Kelvin Y. C. Teo, Theodorus Leonardus Ponsioen, Sioe Lan, Louise OToole, Carolina Arruabarrena Sanchez, Richard Barry, Helena Brosa Morros, Charmaine Chung, Alessandro Invernizzi, Gemmy Chui Ming Cheung, Daniel Barthelmes, Mark C. Gillies

Background

This study aimed to characterise visual acuity (VA) changes in eyes without baseline macular atrophy (MA) that subsequently developed MA during treatment for neovascular age-related macular degeneration (nAMD).

Methods

A case–control analysis was performed using data from a multicentre real-world AMD registry. We compared VA outcomes in 1998 treatment-naïve eyes without MA at baseline and ≥ 5 years of follow-up. Two matched groups (999 eyes each) were analysed: eyes that developed incident MA and those that never did.

Results

Comparisons were made between two matched groups of 999 eyes each with incident MA and those that never developed it with at least 5 years of follow-up. Final VA was best in eyes that never developed MA, followed by eyes that developed extrafoveal and sub-foveal MA (68.9 ± 16.7, 67.0 ± 16.9 and 52.1 ± 23.6 letters, p < 0.01). Eyes with incident MA had more inactive disease visits compared to those that never developed MA. Features associated with poor final VA included the presence of sub-foveal MA (odds ratio [OR] [95% confidence interval (CI)] −16.63 [−18.7 to 14.56], p < 0.01) and a higher proportion of active visits (per 10%) (OR [95% CI] −0.73 [−1.12 to 0.34], p < 0.01). The mean time to lose five letters of vision from first grading of sub-foveal MA was 17.3 ± 4.6 months.

Conclusion

It is important to achieve disease inactivity in nAMD despite its association with incident MA, as neovascular complications play a significant role in VA loss. The long duration between the incidence of MA and clinically significant loss of vision offers an opportunity for potential interventions against atrophy.

背景:本研究旨在描述无基线黄斑萎缩(MA)的眼睛的视力(VA)变化,这些眼睛随后在治疗新生血管性年龄相关性黄斑变性(nAMD)期间发展为MA。方法:使用来自多中心真实世界AMD注册表的数据进行病例对照分析。我们比较了1998年treatment-naïve无MA的眼睛在基线和≥5年随访时的VA结果。研究人员对两组相匹配的眼睛(每组999只眼睛)进行了分析:一组发生偶发性MA的眼睛和一组从未发生过MA的眼睛。结果:在至少5年的随访中,对两组相匹配的999只眼睛进行了比较,每组眼睛有偶发MA和从未发生MA。未发生MA的眼睛的最终VA最好,其次是发生中央凹外和中央凹下MA的眼睛(68.9±16.7,67.0±16.9和52.1±23.6个字母)。结论:尽管与MA事件相关,但在nAMD中实现疾病不活动是重要的,因为新生血管并发症在VA损失中起重要作用。从MA发病到临床上明显的视力丧失之间的长时间间隔为潜在的干预萎缩提供了机会。
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引用次数: 0
Aqueous Humour Concentration of Topically Applied 2.0% Ganciclovir Eye Drops in Eyes With Cytomegalovirus Anterior Uveitis and Endotheliitis: Response 2.0%更昔洛韦滴眼液对巨细胞病毒前葡萄膜炎和内皮炎的治疗效果
IF 5.6 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-07-25 DOI: 10.1111/ceo.14590
Samanthila Waduthantri, Soon Phaik Chee
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引用次数: 0
Optimising Paul Glaucoma Implant Stent Management: Prophylactic Aqueous Suppression, Telemetric IOP Monitoring, and Microfluidic Insights 优化保罗青光眼植入支架管理:预防性水抑制、遥测IOP监测和微流体洞察。
IF 5.6 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-07-23 DOI: 10.1111/ceo.14586
Yuwan Gao
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引用次数: 0
期刊
Clinical and Experimental Ophthalmology
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