Ophthalmology science最新文献

{"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 ,&nbsp;Tsung-Han Chou PhD ,&nbsp;Mascha Louisa Korsch PhD ,&nbsp;Francesco Aiello MD, PhD ,&nbsp;Annagrazia Adornetto PhD ,&nbsp;Rossella Russo PhD ,&nbsp;Giacinto Bagetta MD ,&nbsp;Carlo Nucci MD, PhD ,&nbsp;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> &lt; 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> &lt; 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> &lt; 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> &lt; 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.</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}

{"title":"OCT Angiography of Chorioretinal Microvasculature in Children with Type 1 and Type 2 Diabetes without Retinopathy","authors":"Sarah Aman MBBS ,&nbsp;Melat Asebot MD, MPH ,&nbsp;Dhruva Patel BS ,&nbsp;Elizabeth A. Brown MPH ,&nbsp;Ana Collazo Martinez MPH ,&nbsp;Edward Kuwera MD ,&nbsp;Viet-Hoan Le PhD ,&nbsp;Yi Zhang MS ,&nbsp;Ruikang K. Wang PhD ,&nbsp;Risa M. Wolf MD ,&nbsp;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 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.</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 mm³, <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> &gt; 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}

{"title":"Assessing the Relationship between Foveal Cone Density, Outer Nuclear Layer Thickness and Foveal Morphology","authors":"Serena Zacharias MD ,&nbsp;Joseph Kreis ,&nbsp;Natalie Ungaretti ,&nbsp;Emma Warr ,&nbsp;Heather Heitkotter PhD ,&nbsp;Iniya Adhan MD ,&nbsp;Ashleigh Walesa ,&nbsp;Katherine Hemsworth ,&nbsp;Jenna Grieshop ,&nbsp;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> &lt; 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}

{"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 ,&nbsp;Shiqi Yang MD, PhD ,&nbsp;Qinghuai Liu MD ,&nbsp;Yanping Song MS ,&nbsp;Jianping Tong MD ,&nbsp;Wenbin Wei MD ,&nbsp;Weiqi Chen BS ,&nbsp;Hong Dai MD ,&nbsp;Wei Wang MS ,&nbsp;Miaoqin Wu MD ,&nbsp;Guohong Zhou MD ,&nbsp;Xuan Xiao MD ,&nbsp;Jinglin Zhang MD ,&nbsp;Rongrong Zhu MS ,&nbsp;Haoyu Li MS ,&nbsp;Yafang Wang PhD ,&nbsp;Xiaoyu Chen PhD ,&nbsp;Shujie Lu MS ,&nbsp;Haiwei Du PhD ,&nbsp;Han Han-Zhang PhD ,&nbsp;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}

{"title":"Retinitis Pigmentosa GTPase regulator–Associated Retinal Degeneration: Integrating Patient-Reported Outcomes, Genetic, and Structural Biomarkers","authors":"Nuno Gouveia MD, MSc ,&nbsp;Jessica Karuntu MD ,&nbsp;Hind Almushattat MD ,&nbsp;Rufino Silva MD, PhD ,&nbsp;Camiel Boon MD, PhD ,&nbsp;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}

{"title":"Deep Learning Analysis of Widefield Cornea Endothelial Imaging in Fuchs Dystrophy","authors":"Kai Yuan Tey MBBS ,&nbsp;Brian Juin Hsein Lee MBBS ,&nbsp;Clarissa Ng MBBS ,&nbsp;Qiu Ying Wong ,&nbsp;Satish K. Panda PhD ,&nbsp;Amrit Dash ,&nbsp;Jipson Wong ,&nbsp;Ezekiel Ze Ken Cheong MD ,&nbsp;Jodhbir S. Mehta FRCS(Ed), PhD ,&nbsp;Leopold Schmeterer MSc, PhD ,&nbsp;Khin Yadanar Win PhD ,&nbsp;Damon Wong PhD ,&nbsp;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/mm² vs. manual: 1728.58 ± 805.69 cells/mm², <em>P</em> &lt; 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}

{"title":"OCT-Derived Quantitative Measurement of Extent of Vascularization (“Zone”) in Retinopathy of Prematurity","authors":"David A. Sutter ,&nbsp;Mani K. Woodward ,&nbsp;John Jackson MD ,&nbsp;Yakub Bayhaqi PhD ,&nbsp;Aaron S. Coyner PhD ,&nbsp;Shuibin Ni PhD ,&nbsp;Susan Ostmo MS ,&nbsp;Talita T. Lima MD ,&nbsp;Aaron Nagiel MD, PhD ,&nbsp;Michael F. Chiang MD, MS ,&nbsp;Benjamin K. Young MD, MS ,&nbsp;Yifan Jian PhD ,&nbsp;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 mm², respectively (<em>P</em> &lt; 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> &lt; 0.001) and 80.9 mm² (95% CI: 71.6–90.2) for AVR (<em>P</em> &lt; 0.001). Posterior zone II was intermediate for all measurements. All measures of length and area had an AUROC &gt;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}

{"title":"Can Multimodal Large Language Models Diagnose Diabetic Retinopathy from Fundus Photos? A Quantitative Evaluation","authors":"Jesse A. Most BA ,&nbsp;Evan H. Walker MS ,&nbsp;Nehal N. Mehta MD ,&nbsp;Ines D. Nagel MD ,&nbsp;Jimmy S. Chen MD ,&nbsp;Jonathan F. Russell MD, PhD ,&nbsp;Nathan L. Scott MD, MPP ,&nbsp;Shyamanga Borooah MBBS, PhD","doi":"10.1016/j.xops.2025.100911","DOIUrl":"10.1016/j.xops.2025.100911","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the diagnostic accuracy of 4 multimodal large language models (MLLMs) in detecting and grading diabetic retinopathy (DR) using their new image analysis features.</div></div><div><h3>Design</h3><div>A single-center retrospective study.</div></div><div><h3>Subjects</h3><div>Patients diagnosed with prediabetes and diabetes.</div></div><div><h3>Methods</h3><div>Ultra-widefield fundus images from patients seen at the University of California, San Diego, were graded for DR severity by 3 retina specialists using the ETDRS classification system to establish ground truth. Four MLLMs (ChatGPT-4o, Claude 3.5 Sonnet, Google Gemini 1.5 Pro, and Perplexity Llama 3.1 Sonar/Default) were tested using 4 distinct prompts. These assessed multiple-choice disease diagnosis, binary disease classification, and disease severity. Multimodal large language models were assessed for accuracy, sensitivity, and specificity in identifying the presence or absence of DR and relative disease severity.</div></div><div><h3>Main Outcome Measures</h3><div>Accuracy, sensitivity, and specificity of diagnosis.</div></div><div><h3>Results</h3><div>A total of 309 eyes from 188 patients were included in the study. The average patient age was 58.7 (56.7–60.7) years, with 55.3% being female. After specialist grading, 70.2% of eyes had DR of varying severity, and 29.8% had no DR. For disease identification with multiple choices provided, Claude and ChatGPT scored significantly higher (<em>P</em> &lt; 0.0006, per Bonferroni correction) than other MLLMs for accuracy (0.608–0.566) and sensitivity (0.618–0.641). In binary DR versus no DR classification, accuracy was the highest for ChatGPT (0.644) and Perplexity (0.602). Sensitivity varied (ChatGPT [0.539], Perplexity [0.488], Claude [0.179], and Gemini [0.042]), whereas specificity for all models was relatively high (range: 0.870–0.989). For the DR severity prompt with the best overall results (Prompt 3.1), no significant differences between models were found in accuracy (Perplexity [0.411], ChatGPT [0.395], Gemini [0.392], and Claude [0.314]). All models demonstrated low sensitivity (Perplexity [0.247], ChatGPT [0.229], Gemini [0.224], and Claude [0.184]). Specificity ranged from 0.840 to 0.866.</div></div><div><h3>Conclusions</h3><div>Multimodal large language models are powerful tools that may eventually assist retinal image analysis. Currently, however, there is variability in the accuracy of image analysis, and diagnostic performance falls short of clinical standards for safe implementation in DR diagnosis and grading. Further training and optimization of common errors may enhance their clinical utility.</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 100911"},"PeriodicalIF":4.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097868","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":"Pigmentary Maculopathy in Patients with Interstitial Cystitis: Association with Pentosan Polysulfate and Other Therapies","authors":"Sunny Qin MD ,&nbsp;Joni K. Evans MS ,&nbsp;Chaewon Jeong MD ,&nbsp;Margaret Havunjian MD ,&nbsp;Nieraj Jain MD ,&nbsp;Margaret A. Greven MD ,&nbsp;Sally S. Ong MD","doi":"10.1016/j.xops.2025.100909","DOIUrl":"10.1016/j.xops.2025.100909","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To examine the association between the development of pigmentary maculopathy and exposure to pentosan polysulfate sodium (PPS) and other therapies in patients with interstitial cystitis (IC).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Single-center retrospective study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;div&gt;Patients diagnosed with IC who had ≥2 eye examinations at Wake Forest School of Medicine between January 2011 and August 2021.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Two masked retina specialists evaluated available multimodal imaging for pigmentary maculopathy using the established criteria, with any disagreements adjudicated by a third reviewer. Cases were categorized by severity and analyzed for associations with medication exposure.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Association between the development of pigmentary maculopathy with PPS exposure duration and cumulative dose, and concurrent IC medication use.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 336 patients with IC (176 with PPS exposure, 160 without) were included. Patients with PPS exposure had increased odds of exposure to hydroxyzine (odds ratio [OR]: 4.76, &lt;em&gt;P&lt;/em&gt; &lt; 0.0001), amitriptyline (OR: 2.62, &lt;em&gt;P&lt;/em&gt; &lt; 0.0002), phenazopyridine or pyridium (OR: 1.68, &lt;em&gt;P&lt;/em&gt; = 0.036), narcotics (OR: 2.68, &lt;em&gt;P&lt;/em&gt; &lt; 0.0001), oxybutynin (OR: 1.93, &lt;em&gt;P&lt;/em&gt; = 0.041), cystoscopy with hydrodistention (OR: 4.001, &lt;em&gt;P&lt;/em&gt; &lt; 0.0001), bladder instillation (OR: 6.83, &lt;em&gt;P&lt;/em&gt; &lt; 0.0001), and vaginal valium (OR: 9.515, &lt;em&gt;P&lt;/em&gt; = 0.033). Of the 122 patients with retinal imaging (71 with PPS exposure, 51 without), 8 patients (16 eyes) were graded to have pigmentary maculopathy and all 8 patients had PPS exposure. The median duration of PPS exposure in patients with moderate/severe maculopathy was 121 months (interquartile range [IQR] 117, 121) with a median cumulative dose of 929 200 mg (IQR 799 200; 1 109 100), which were significantly higher than patients with mild or no maculopathy (median duration 35 months [IQR 10, 63], &lt;em&gt;P&lt;/em&gt; = 0.002 and median dose 166 800 mg [IQR 44 600; 569 100], &lt;em&gt;P&lt;/em&gt; = 0.004). Higher proportions of patients with pigmentary maculopathy than those without had concurrent exposure to PPS and amitriptyline/nortriptyline (75% vs. 34.9%, &lt;em&gt;P&lt;/em&gt; = 0.015) or PPS and cyclosporine (37.5% vs. 1.6%, &lt;em&gt;P&lt;/em&gt; = 0.003).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Pentosan polysulfate sodium exposure, and not IC itself, was associated with the development of pigmentary maculopathy. Longer duration and higher cumulative dose were associated with worse maculopathy. Patients on PPS were more likely to be on multiple other therapies for IC. Concurrent exposure to PPS and amitriptyline/nortriptyline or cyclosporine may increase the risk of developing maculopathy but these results should be validated by larger prospective studies.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Financial Disclosure(s)&lt;/h3&gt;&lt;div&gt;Proprietary or commercial disc","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100909"},"PeriodicalIF":4.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109329","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":"Comparison of Deep Optic Nerve Head Structures and Optic Disc Morphology in Unilateral Peripapillary Intrachoroidal Cavitation","authors":"Kaho Akiyama MD ,&nbsp;Shuichiro Aoki MD ,&nbsp;Shiroaki Shirato MD, PhD ,&nbsp;Rei Sakata MD, PhD ,&nbsp;Megumi Honjo MD, PhD ,&nbsp;Makoto Aihara MD, PhD ,&nbsp;Hitomi Saito MD, PhD","doi":"10.1016/j.xops.2025.100908","DOIUrl":"10.1016/j.xops.2025.100908","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare background characteristics, deep optic nerve head (ONH) structures, and optic disc morphology in participants with unilateral peripapillary intrachoroidal cavitation (PICC).</div></div><div><h3>Design</h3><div>Retrospective cross-sectional study.</div></div><div><h3>Participants</h3><div>One hundred six eyes of 53 participants with unilateral PICC determined on OCT.</div></div><div><h3>Methods</h3><div>Twelve ONH-centered OCT radial slices were used to manually measure Bruch membrane opening (BMO) area, BMO ovality, scleral flange opening (SFO) area, SFO ovality, and SFO/BMO offset magnitude which represents the degree of SFO/BMO centroid displacement and clinically corresponds to the peripapillary atrophy–gamma and delta zones. Optic disc tilt, rotation, area, and longest and shortest diameters were measured from line scanning laser ophthalmoscopy images.</div></div><div><h3>Main Outcome Measures</h3><div>Paired <em>t</em> tests and Wilcoxon signed-rank tests were used to compare background characteristics and obtained parameters between PICC eyes and their contralateral eyes. False discovery rate was controlled using the Benjamini–Hochberg method to account for multiple comparisons.</div></div><div><h3>Results</h3><div>Peripapillary intrachoroidal cavitation eyes showed significantly larger BMO area (<em>P</em> &lt; 0.001) and its ovality (<em>P</em> = 0.020), larger SFO area (<em>P</em> = 0.003), larger SFO/BMO offset magnitude (<em>P</em> = 0.007), greater optic disc tilt (<em>P</em> &lt; 0.001), and smaller optic disc shortest diameter (<em>P</em> = 0.010). There was no significant difference in axial length (AL) (<em>P</em> = 0.081) and optic disc rotation (<em>P</em> = 0.067).</div></div><div><h3>Conclusions</h3><div>Although AL was similar between PICC eyes and their contralateral eyes, significant intereye differences in deep ONH structures and optic disc morphology were observed. Peripapillary intrachoroidal cavitation eyes exhibited a more elliptically expanded BMO, larger SFO, greater SFO/BMO misalignment, and greater optic disc tilt, which are structural changes associated with border tissue elongation. Our findings indicate a strong association between the presence of PICC and myopia-related characteristic deep ONH remodeling, providing a foundation for understanding structural abnormalities in myopic eyes.</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 100908"},"PeriodicalIF":4.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050610","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}