Ophthalmology science最新文献

{"title":"Lacquer Cracks Detection and Measurement Using Black-on-White Infrared Reflectance and Late-Phase Indocyanine Green Angiography in Pathologic Myopia","authors":"Matteo Maria Girolamo MD ,&nbsp;Emanuele Crincoli MD ,&nbsp;Francesca Amoroso MD ,&nbsp;Juliana Estrada-Walker MD ,&nbsp;Giuseppe Querques MD, PhD ,&nbsp;Eric H. Souied MD, PhD ,&nbsp;Alexandra Miere MD, PhD","doi":"10.1016/j.xops.2025.100987","DOIUrl":"10.1016/j.xops.2025.100987","url":null,"abstract":"<div><h3>Purpose</h3><div>The aim of this study is to compare the detection and quantification of lacquer cracks (LCs) using 2 imaging methods: indocyanine green angiography (ICGA) and black-on-white infrared reflectance (bwIR).</div></div><div><h3>Design</h3><div>Retrospective single-center study.</div></div><div><h3>Subjects</h3><div>Myopic patients diagnosed with LCs at the Department of Ophthalmology of the University Paris Est Créteil.</div></div><div><h3>Methods</h3><div>Medical records and multimodal imaging, including bwIR and ICGA, of myopic patients aged &gt;18 years with LCs were reviewed. Two independent graders evaluated the presence of LCs in bwIR images and on late-phase ICGA. Image processing was used to segment and compute the area of LCs on bwIR and ICGA.</div></div><div><h3>Main Outcome Measures</h3><div>Evaluation and comparison of the rate of detection of LCs on bwIR and late-phase ICGA. Comparison between the extent of LCs detected by bwIR and with late-phase ICGA.</div></div><div><h3>Results</h3><div>Thirty-two (32) eyes of 22 patients (13 women, 9 men) with a mean age of 54.95 ± 18.7 years were included in this study. Graders detected LCs on bwIR images in 29/32 analyzed cases (90.6% sensitivity, 95% CI: 75%–98%), whereas they detected LCs in 32/32 cases in ICGA images (100% sensitivity). Agreement between graders in detection was very good (Cohen κ = 0.78). The mean area of the LCs detected in bwIR images was 14.58 ± 8.21 mm², whereas the mean area of the LCs in ICGA was 13.86 ± 8.50 mm². This difference was not statistically significant in paired analysis (<em>P</em> = 0.73).</div></div><div><h3>Conclusions</h3><div>In this study, we propose rapid and noninvasive bwIR as a valid and promising noninvasive screening tool for detection of LCs and quantifying their extension.</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 100987"},"PeriodicalIF":4.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618261","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":"Association between Baseline Subfoveal Choroidal Thickness and Anatomical and Functional Outcomes in Geographic Atrophy","authors":"Alythia Vo BS ,&nbsp;Liangbo Linus Shen MD ,&nbsp;Irene Pak BS ,&nbsp;Abu Tahir Taha BS ,&nbsp;Antonio Z. Diaz BS ,&nbsp;Jay M. Stewart MD","doi":"10.1016/j.xops.2025.100986","DOIUrl":"10.1016/j.xops.2025.100986","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the relationship between baseline subfoveal choroidal thickness (SFChT) and both visual outcomes and geographic atrophy (GA) growth rate, and to assess whether SFChT mediates the treatment effect of oral metformin on GA progression.</div></div><div><h3>Design</h3><div>Secondary analysis of a randomized controlled trial.</div></div><div><h3>Participants</h3><div>Seventy eyes (34 metformin; 36 observation) from 44 participants (21 metformin; 23 observation) with GA and ≥6 months of follow-up in the METformin for the MINimization of Geographic Atrophy Progression study.</div></div><div><h3>Methods</h3><div>Subfoveal choroidal thickness was measured from baseline OCT. We calculated GA area growth rate by subtracting the GA area at the first visit from the GA area at the last visit and dividing the result by the time interval. Geographic atrophy perimeter-adjusted growth rate was calculated by dividing GA area growth rate by the mean GA perimeter between the first and last visit.</div></div><div><h3>Main Outcome Measures</h3><div>Longitudinal changes in GA area and visual acuity.</div></div><div><h3>Results</h3><div>Baseline SFChT was not significantly associated with baseline GA area (<em>P</em> = 0.51), baseline best-corrected visual acuity (BCVA) (<em>P</em> = 0.49), baseline low-luminance visual acuity (LLVA) (<em>P</em> = 0.85), or rim area focal hyperautofluorescence signals (<em>P</em> = 0.29). Baseline SFChT was not significantly associated with GA perimeter-adjusted growth rate (<em>P</em> = 0.74), the decline rate of BCVA (<em>P</em> = 0.14), and the decline rate of LLVA (<em>P</em> = 0.71). However, sensitivity analyses in GA subgroups found that baseline SFChT was associated with decreased rate of BCVA decline in patients with foveal-involving GA (Spearman ρ = 0.03, <em>P</em> = 0.03). Baseline SFChT did not significantly influence the effect of oral metformin on GA perimeter-adjusted growth rate (<em>P</em> = 0.78).</div></div><div><h3>Conclusions</h3><div>Greater baseline SFChT was significantly associated with slower BCVA decline in eyes with foveal-involving GA, suggesting a possible localized role of choroidal thickness in preserving central vision. However, SFChT was not associated with GA growth rate, LLVA decline, or baseline anatomical and functional measures. It also did not mediate the effect of oral metformin. While SFChT lacks prognostic value for GA progression overall, it may hold limited relevance for central vision outcomes in foveal-involving GA.</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 2","pages":"Article 100986"},"PeriodicalIF":4.6,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145694610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Reticular Pseudodrusen on Clinical and Ocular Characteristics and Progression Rate of Geographic Atrophy in Japanese Patients","authors":"Naoko Ueda-Arakawa MD, PhD ,&nbsp;Yukiko Sato MD, PhD ,&nbsp;Masahiro Miyake MD, PhD ,&nbsp;Ayako Takahashi MD, PhD ,&nbsp;Yuki Mori MD, PhD ,&nbsp;Yasunori Miyara MD ,&nbsp;Chikako Hara MD, PhD ,&nbsp;Yoko Kitajima MD ,&nbsp;Ruka Maruko MD, PhD ,&nbsp;Moeko Kawai MD ,&nbsp;Masayuki Ohnaka MD, PhD ,&nbsp;Hideki Koizumi MD, PhD ,&nbsp;Maiko Maruyama-Inoue MD, PhD ,&nbsp;Yasuo Yanagi MD, PhD ,&nbsp;Tomohiro Iida MD, PhD ,&nbsp;Mineo Kondo MD, PhD ,&nbsp;Taiji Sakamoto MD, PhD ,&nbsp;Akitaka Tsujikawa MD, PhD","doi":"10.1016/j.xops.2025.100984","DOIUrl":"10.1016/j.xops.2025.100984","url":null,"abstract":"<div><h3>Purpose</h3><div>To elucidate the impact of reticular pseudodrusen (RPD) on the clinical and ocular characteristics and progression rate of geographic atrophy (GA) in Japanese patients.</div></div><div><h3>Design</h3><div>A multicenter, retrospective, observational cohort study.</div></div><div><h3>Participants</h3><div>A total of 173 eyes from 173 Japanese patients (135 with conventional GA and 35 with pachychoroid GA) were included; 79 eyes with conventional GA were included in the follow-up group.</div></div><div><h3>Methods</h3><div>Reticular pseudodrusen status, GA type (conventional/pachychoroid), GA location (central/noncentral), GA pattern (unifocal/multifocal), subfoveal choroidal thickness (SFCT), and fellow-eye status were assessed using multimodal imaging. The GA progression rate was calculated in both mm²/year and mm/year (square root transformation [SQRT]) after semiautomatic measurement of the GA area on fundus autofluorescence images.</div></div><div><h3>Main Outcome Measures</h3><div>Clinical and ocular characteristics and progression rate of GA according to RPD status.</div></div><div><h3>Results</h3><div>Reticular pseudodrusen were observed in 42.4% (73 eyes) of the 173 study eyes, 54.1% of the eyes with conventional GA, and none of the eyes with pachychoroid GA. Among patients with conventional GA, those with RPD were significantly more female (56.2 vs. 30.6%, <em>P</em> = 0.003), had better visual acuity (0.31 vs. 0.50 in logarithm of the minimum angle of resolution, <em>P</em> = 0.03), a smaller SFCT (141.7 vs. 185.0 μm, <em>P</em> = 0.02), higher prevalence of noncentral (56.2 vs. 32.3%, <em>P</em> = 0.005) and multifocal GA (68.5 vs. 29.0%, <em>P</em> &lt; 0.001), and bilateral late age-related macular degeneration (AMD) (93.1 vs. 65.0%, <em>P</em> &lt; 0.0001) than those without RPD. The GA progression rate was significantly higher in eyes with RPD than in eyes without RPD (0.34 vs. 0.18 mm/year [SQRT], <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Reticular pseudodrusen are frequently observed in Japanese patients with conventional GA. Clinical and ocular characteristics differ according to the RPD status, similarly in White patients. Geographic atrophy in the presence of RPD progresses rapidly, at a rate comparable to that in White patients, and most patients with RPD exhibit bilateral late AMD. Given that RPD in eyes with GA constitutes a strong risk factor for both fast GA progression and bilateral late AMD, GA with RPD should be treated at an early stage prior to foveal involvement, even though GA in Asians has been reported to progress slowly.</div></div><div><h3>Financial Disclosures</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 2","pages":"Article 100984"},"PeriodicalIF":4.6,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645982","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":"Attention-Based Multimodal Deep Learning for Uveal Melanoma Classification Using Ultra-Widefield Fundus Images and Ocular Ultrasound","authors":"Albert K. Dadzie OD ,&nbsp;Sabrina P. Iddir MD ,&nbsp;Mansour Abtahi PhD ,&nbsp;Behrouz Ebrahimi MSc ,&nbsp;Mojtaba Rahimi MSc ,&nbsp;Sanjay Ganesh BS ,&nbsp;Taeyoon Son PhD ,&nbsp;Michael J. Heiferman MD ,&nbsp;Xincheng Yao PhD","doi":"10.1016/j.xops.2025.100985","DOIUrl":"10.1016/j.xops.2025.100985","url":null,"abstract":"<div><h3>Purpose</h3><div>To develop and evaluate a deep learning model that integrates ultra-widefield fundus photography and B-scan ultrasonography for automated classification of uveal melanoma (UM) and choroidal nevi.</div></div><div><h3>Design</h3><div>A retrospective cross-sectional study.</div></div><div><h3>Subjects</h3><div>This study included 174 patients (93 with UM and 81 with choroidal nevi) diagnosed at a tertiary eye center. For each patient, ultra-widefield fundus photographs and B-scan ultrasound images in both transverse and longitudinal orientations were acquired.</div></div><div><h3>Methods</h3><div>A deep learning model was trained using ultra-widefield fundus photography, ultrasound images, and combinations of both. Fivefold cross-validation was used to evaluate model performance.</div></div><div><h3>Main Outcome Measures</h3><div>The deep learning models were evaluated using accuracy, F1 score, and area under the receiver operating characteristic curve (AUC).</div></div><div><h3>Results</h3><div>Uveal melanomas had a mean thickness of 6.0 mm and a basal diameter of 12.6 mm, whereas nevi measured 1.8 mm and 6.5 mm, respectively. Among single-modality models, the model trained on transverse ultrasound images achieved the highest performance (accuracy: 92%; F1 score: 0.9227; AUC: 0.9538). Averaging predictions from the single-modality models provided only modest gains because their outputs sometimes conflicted. In contrast, the model that combined fundus photographs and ultrasound images using an attention mechanism achieved the highest overall performance (accuracy: 94%; F1 score: 0.9445; AUC: 0.9606), outperforming all other configurations by effectively integrating complementary information from both modalities.</div></div><div><h3>Conclusions</h3><div>Multimodal deep learning that combines fundus photography and ultrasound imaging improves the classification of UM and choroidal nevi. This approach demonstrates feasibility for leveraging the strengths of each modality for automated classification of UM and choroidal nevi.</div></div><div><h3>Financial Disclosures</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 2","pages":"Article 100985"},"PeriodicalIF":4.6,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645983","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":"OCT Angiography–Based Quantitative Choroidal Vasculature Analysis in Choroidal Melanomas and Nevi","authors":"Tekla Kurdiani,&nbsp;Miltiadis Fiorentzis MD,&nbsp;Nikolaos E. Bechrakis MD,&nbsp;Tobias Kiefer MD","doi":"10.1016/j.xops.2025.100979","DOIUrl":"10.1016/j.xops.2025.100979","url":null,"abstract":"<div><h3>Purpose</h3><div>Differentiation between choroidal melanoma (CM) and choroidal nevus (CN) is primarily made clinically with the aid of multimodal imaging. Both entities can be distinguished by their vascular architecture in histopathology. OCT angiography (OCT-A) is a noninvasive method to visualize retinal and choroidal vasculature and has rarely been used to differentiate CM and CN, and if so, exclusively descriptively. The purpose of this study was to differentiate both entities via OCT-A using an open-source vascular analysis software (OCTAVA), using quantitative choroidal vasculature analysis.</div></div><div><h3>Design</h3><div>Retrospective case-control study.</div></div><div><h3>Subjects</h3><div>Treatment-naïve patients with CM and CN who obtained OCT-A of the tumor at the University Hospital Essen between November 2022 and December 2024.</div></div><div><h3>Methods</h3><div>Choroidal OCT-A sections were analyzed using an ImageJ-based open-source software (OCTAVA).</div></div><div><h3>Main Outcome Measures</h3><div>To assess the comparison between CM and CN using vessel area density, vessel length density, total vessel length, mean vessel diameter, and tortuosity index.</div></div><div><h3>Results</h3><div>Thirty patients with CM and 30 patients with CN could be included in the study. Choroidal melanoma showed significantly reduced vessel area density (30.46% vs. 37.10%; <em>P</em> &lt; 0.001), vessel length density (1.83% vs. 2.40%; <em>P</em> &lt; 0.001), total vessel length (11.8 vs. 19.7 mm; <em>P</em> &lt; 0.001), and tortuosity index (0.140 vs. 0.155; <em>P</em> = 0.008) compared with CN, whereas vessel diameter showed no significant difference. Receiver operating curve analysis demonstrated good diagnostic performance for vessel area density, vessel length density, and total vessel length (area under the curve: 0.81–0.86).</div></div><div><h3>Conclusions</h3><div>OCT angiography using open-source software quantitative choroidal vasculature analysis may play a future role in objective differentiation between CM and CN. Future role of OCT-A in multimodal imaging for melanocytic choroidal tumors must, however, be further validated in larger, prospective trials and across different, preferably commercially available OCT platforms.</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 100979"},"PeriodicalIF":4.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684241","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":"Macular Thickness and Its Associated Factors in a Healthy Cynomolgus Colony: The Non-Human Primates Eye Study","authors":"Hongyi Liu PhD ,&nbsp;Simeng Hou PhD ,&nbsp;Sirui Zhu PhD ,&nbsp;Weihai Liu MD ,&nbsp;Moksada Regmi PhD ,&nbsp;Chenlong Yang MD ,&nbsp;Jian Wu PhD ,&nbsp;Ningli Wang MD, PhD","doi":"10.1016/j.xops.2025.100981","DOIUrl":"10.1016/j.xops.2025.100981","url":null,"abstract":"<div><h3>Purpose</h3><div>The research aims to investigate the normal macular thickness range in a healthy cynomolgus colony and examine its association with relevant parameters.</div></div><div><h3>Design</h3><div>Cross-sectional observational study.</div></div><div><h3>Subjects</h3><div>A total of 418 healthy cynomolgus monkeys (mean age, 13.22 ± 7.86 years; range, 1–29 years) from the Non-Human Primates Eye Study conducted between 2021 and 2022.</div></div><div><h3>Methods</h3><div>All included monkeys underwent comprehensive ocular measurements, including macular thickness measurement using spectral-domain OCT. To account for the correlation between eyes, generalized linear mixed models were applied. To assess the gender differences in macular thickness and volume, independent T-tests were employed. Linear regression, including quadratic terms (Age²), was used to examine the relationships between macular subregions and age. Additionally, univariate analyses and multivariate linear regression were conducted to evaluate the associations between the central, average inner ring, and average outer macular thickness and various systemic and ophthalmic parameters.</div></div><div><h3>Main Outcome Measures</h3><div>Macular thickness in ETDRS subfields and its associations with age and ocular parameters.</div></div><div><h3>Results</h3><div>Sex statistically significant differences were observed only in the superior sector of the inner ring and in the temporal sector of the outer ring after adjustment. In inner rings, all 4 subfields exhibited a significant age-related decline; meanwhile, temporal and superior subfields decreased with increasing age in the outer ring. After adjustment, macular thickness was independently associated with age and end-of-anesthesia intraocular pressure (IOP) in the central region, axial length (AXL) in the average inner ring, AXL and mid-anesthesia IOP in the average outer ring, and AXL and end-of-anesthesia IOP for the overall average thickness.</div></div><div><h3>Conclusions</h3><div>This study provided valuable reference data on macular thickness in different ages and sexes of cynomolgus which could be utilized in preclinical nonhuman primate experiments.</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 100981"},"PeriodicalIF":4.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789911","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: Sim et al: Additive Effect of Highly Aspherical Lenslet Target Spectacles to Children Inadequately Controlled by Atropine","authors":"Hakan Kaymak MD ,&nbsp;Berthold Seitz MD ,&nbsp;Michael Bärtschi PhD ,&nbsp;Machteld Devenijn","doi":"10.1016/j.xops.2025.100982","DOIUrl":"10.1016/j.xops.2025.100982","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100982"},"PeriodicalIF":4.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145579186","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":"CTx001 for Geographic Atrophy: A Gene Therapy Expressing Soluble, Truncated Complement Receptor 1 (Mini-CR1)","authors":"Sonika Rathi PhD ,&nbsp;Athanasios Didangelos PhD ,&nbsp;Sofiya Pisarenka PhD ,&nbsp;Rachel Green ,&nbsp;Stamatia Zafeiri ,&nbsp;Peter Emery-Billcliff MSc ,&nbsp;Nakul Patel PhD ,&nbsp;Pamela Whalley ,&nbsp;Parisa Zamiri MD, PhD ,&nbsp;Viranga Tilakaratna ,&nbsp;Ewa Szula PhD ,&nbsp;Rafiq Hasan MD ,&nbsp;Mustafa M. Munye PhD ,&nbsp;Richard D. Unwin PhD ,&nbsp;Paul N. Bishop MD, PhD ,&nbsp;Dennis Keefe PhD ,&nbsp;Simon J. Clark DPhil","doi":"10.1016/j.xops.2025.100980","DOIUrl":"10.1016/j.xops.2025.100980","url":null,"abstract":"<div><h3>Purpose</h3><div>Preclinical evaluation of a novel gene therapy called CTx001 for treating geographic atrophy (GA). CTx001 encodes a protein called mini-CR1, which is a soluble fragment of complement receptor 1.</div></div><div><h3>Design</h3><div>CTx001 was used in vitro and in vivo to analyze expression and complement-modulating activity. Mini-CR1 was used in vitro to analyze complement-modulating activity, and its ability to cross human Bruch’s membrane was evaluated ex vivo.</div></div><div><h3>Participants</h3><div>CTx001, which is a self-complementary rAAV2 gene therapy vector expressing mini-CR1. Recombinant mini-CR1 protein, retinal pigment epithelium (RPE) cell lines, serum, human donor Bruch’s membrane, and a rat model.</div></div><div><h3>Methods</h3><div>Recombinant mini-CR1 protein was produced in mammalian cells and purified. C3b and C4b breakdown assays were performed. Wieslab assays measured complement regulatory activity in serum. Mini-CR1 binding to C3b was measured using biolayer interferometry. The diffusion of mini-CR1 across human Bruch’s membrane was assessed using an Ussing chamber. Retinal pigment epithelium cell lines were transduced with CTx001 to assess expression, including directionality and complement modulatory activity. In vivo efficacy of CTx001 was tested using a rat laser–induced choroidal neovascularization (CNV) model.</div></div><div><h3>Main Outcome Measures</h3><div>C3b/iC3b/C4b degradation, inhibition of membrane attack complex (MAC) formation in human serum, mini-CR1 binding to C3b, vector transduction efficiency, protein secretion and localization, and complement inhibition in vivo.</div></div><div><h3>Results</h3><div>Mini-CR1 demonstrated potent cofactor activity for factor I–mediated cleavage of C3b, iC3b, and C4b; therefore, it inhibits both the alternative and classical complement pathways. It inhibited complement activation with an IC₅₀ of 125 nM in human serum. Mini-CR1 demonstrated high-affinity binding to C3b. The mini-CR1 protein diffused across human Bruch’s membrane and retained activity postdiffusion. CTx001-transduced RPE cells secreted mini-CR1 apically and basolaterally, leading to reduced C3 activation and MAC deposition. In rats, subretinal administration of CTx001 resulted in a 75.4% reduction in MAC deposition in CNV lesions (<em>P</em> &lt; 0.01).</div></div><div><h3>Conclusions</h3><div>CTx001 is a potent inhibitor of complement. It efficiently transduces RPE cells, resulting in apical and basolateral secretion and crosses Bruch’s membrane, so it is expected to deliver mini-CR1 to the retina and choroid. These findings support its further development as a 1-time gene therapy for addressing complement overactivation in GA.</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 100980"},"PeriodicalIF":4.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618174","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":"Biomarker-Specific Test-Retest Repeatabilities of Microperimetry in Neovascular Age-Related Macular Degeneration","authors":"Laetitia Hinterhuber ,&nbsp;Klaudia Birner MD ,&nbsp;Johannes Schrittwieser MD ,&nbsp;Leonard M. Coulibaly MD ,&nbsp;Philipp Fuchs MD ,&nbsp;Simon Schürer-Waldheim MSc ,&nbsp;Markus Gumpinger MSc ,&nbsp;Hrvoje Bogunovic PhD ,&nbsp;Ursula Schmidt-Erfurth MD ,&nbsp;Gregor S. Reiter MD, PhD","doi":"10.1016/j.xops.2025.100978","DOIUrl":"10.1016/j.xops.2025.100978","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the biomarker-specific intradevice and interdevice repeatability of microperimetry (MP) examinations in patients with neovascular age-related macular degeneration (nAMD).</div></div><div><h3>Design</h3><div>Cross-sectional study.</div></div><div><h3>Subjects</h3><div>Twenty eyes of 20 individuals with nAMD.</div></div><div><h3>Methods</h3><div>Patients underwent 2 consecutive MP assessments on the MP-3 (photopic) and Macular Integrity Assessment ([MAIA], mesopic), each in a randomized sequence. The pointwise sensitivity values were obtained using a 45-stimuli grid and were coregistered with the OCT volumes. Intraretinal fluid (IRF), subretinal fluid, and pigment epithelium detachment (PED) were quantified with deep learning, whereas subretinal hyperreflective material (SHRM) and ellipsoid zone (EZ) loss were manually annotated. Intradevice repeatability was assessed using Bland–Altman plots, coefficient of repeatability (CoR) and intraclass correlation coefficient. Differences in fixation stability and examination time were calculated using mixed-effect models.</div></div><div><h3>Main Outcome Measures</h3><div>Intradevice and interdevice repeatability and impact of OCT biomarkers on repeatability</div></div><div><h3>Results</h3><div>Analysis of a total of 3600 stimuli points revealed a CoR of ±6.37 decibel and ±5.68 for MP-3 and MAIA, respectively. Presence of OCT biomarkers had a significant impact on repeatability in the MP-3 for IRF (<em>P</em> &lt; 0.0001), SHRM (<em>P</em> = 0.015), and EZ loss (<em>P</em> &lt; 0.0001). Statistically significant results were obtained in the MAIA for IRF (<em>P</em> &lt; 0.0001), PED (<em>P</em> &lt; 0.0001), SHRM (<em>P</em> = 0.0005), and EZ loss (<em>P</em> &lt; 0.0001). Intraclass correlation coefficients revealed excellent intradevice repeatability and good interdevice repeatability, ranging from 0.83 [95% confidence interval [CI]: 0.60–0.91] to 0.94 [95% CI: 0.93–0.94].</div></div><div><h3>Conclusions</h3><div>OCT biomarkers IRF, SHRM, and EZ loss significantly impacted repeatability under photopic and mesopic testing conditions with the MAIA also revealing a statistically significant association for PED. These findings demonstrate the viability of the MP devices to detect functional variability associated with nAMD biomarkers. Repeatability between consecutive MP tests in 2 commonly used MP devices showed good-to-excellent metrics in nAMD, which further supports the use of MP as a viable outcome measure in clinical trials and practice.</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 100978"},"PeriodicalIF":4.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145579185","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":"Structural Biomarkers Influencing Drusenoid Pigment Epithelial Detachment Lifecycle and the Development of Late Macular Degeneration","authors":"Serena Fragiotta MD, PhD ,&nbsp;Giuseppe Querques MD, PhD ,&nbsp;Maria Sole Polito MD ,&nbsp;Eliana Costanzo MD ,&nbsp;Tommaso Rossi MD ,&nbsp;Monica Varano MD ,&nbsp;Francesca Maria Pannarale MD ,&nbsp;Yoichi Sakurada MD ,&nbsp;Mariacristina Parravano MD","doi":"10.1016/j.xops.2025.100977","DOIUrl":"10.1016/j.xops.2025.100977","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;A retrospective cohort study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants&lt;/h3&gt;&lt;div&gt;Patients with dPED in the setting of AMD.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;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).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;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, &lt;em&gt;P&lt;/em&gt; = 0.002) and the presence of hyperreflective foci (HRF) at baseline (HR: 6.6, 95% CI: 1.97–22, &lt;em&gt;P&lt;/em&gt; = 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, &lt;em&gt;P&lt;/em&gt; = 0.01) of MNV development, while HRF (sHR = 6.69, 95% CI: 1.98–22.61, &lt;em&gt;P&lt;/em&gt; = 0.002) and external limiting membrane disruption at baseline (sHR = 3.69, 95% CI: 1.03–13.14, &lt;em&gt;P&lt;/em&gt; = 0.044) were factors significantly associated with increased GA risk.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;","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}