Ophthalmology science最新文献

{"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":"2026-01-01","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":"Association of Physical Frailty and Genetic Predisposition with Risk of Irreversible Eye Diseases","authors":"Zhenyi Xu PhD ,&nbsp;Ruilang Lin MMed ,&nbsp;Xiaojun Wang PhD ,&nbsp;Yahang Liu ,&nbsp;Chen Huang PhD ,&nbsp;Ce Wang PhD ,&nbsp;Zhijun Bao PhD","doi":"10.1016/j.xops.2025.100910","DOIUrl":"10.1016/j.xops.2025.100910","url":null,"abstract":"<div><h3>Objective</h3><div>The evidence linking frailty to overall and specific irreversible eye diseases is limited. Moreover, it is unclear whether frailty is associated with similar increased risk across individuals with different genetic risk profiles. The aim of this study was to examine the association between frailty and overall and specific irreversible eye diseases and explore the modification effect of genetic risk of glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) in such associations.</div></div><div><h3>Design</h3><div>Prospective cohort study.</div></div><div><h3>Participants</h3><div>The study included a total of 409 579 White participants in the UK Biobank study.</div></div><div><h3>Methods</h3><div>Physical frailty was defined by 5 components: weight loss, exhaustion, low physical activity, slow walking speed, and low grip strength. Participants were classified as nonfrail, prefrail, or frail. Polygenic risk score was categorized as low (tertile 1), intermediate (tertile 2), or high (tertile 3). Cox regression was used to assess the association of physical frailty with irreversible eye diseases.</div></div><div><h3>Main Outcomes and Measures</h3><div>Irreversible eye diseases were identified using hospital admission electronic health records and death registries.</div></div><div><h3>Results</h3><div>Among 409 579 individuals (mean age, 56.5 years; 46.5% male) with a median follow-up of 13.1 years, 10 927, 7 095, and 919 were diagnosed with irreversible eye disease in the nonfrail, prefrail, and frail groups, respectively. Prefrail and frail individuals showed increased risks of overall irreversible eye diseases, with a 12% higher risk for prefrail individuals (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.09–1.16) and a 47% higher risk for frail individuals (HR, 1.47; 95% CI, 1.37–1.58). Increased risks were also observed for specific irreversible eye diseases, including glaucoma (HR, 1.11 [95% CI, 1.06–1.17] for prefrailty; HR, 1.43 [95% CI, 1.28–1.61] for frailty), diabetic retinopathy (HR, 1.12 [95% CI, 1.03–1.21] for prefrailty; HR, 1.53 [95% CI, 1.34–1.73] for frailty), and AMD (HR, 1.13 [95% CI, 1.08–1.19] for prefrailty; HR, 1.35 [95% CI, 1.20–1.52] for frailty). Furthermore, individuals with more severe frailty status and higher genetic risk exhibited higher risks of irreversible eye diseases than those with low genetic risk and nonfrailty.</div></div><div><h3>Conclusions</h3><div>Frailty was associated with an increased risk of irreversible eye diseases, particularly among individuals with higher genetic risk. These findings suggest that targeted strategies to prevent and manage frailty may contribute to reducing the risk of irreversible eye diseases.</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 100910"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159825","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":"Retinal Perfusion and Injury in Sepsis and after Major Surgery","authors":"Ella Courtie PhD ,&nbsp;Gagana Mallawaarachchi MBChB ,&nbsp;Aditya U. Kale MBChB ,&nbsp;Ahmed Gilani FRCA ,&nbsp;Nicholas Capewell ,&nbsp;Donna Holding ,&nbsp;Benjamin T.K. Hui BMBS ,&nbsp;Xiaoxuan Liu PhD ,&nbsp;Elinor Laws MBChB ,&nbsp;Ann Logan PhD ,&nbsp;Tony Whitehouse MD ,&nbsp;Alastair K. Denniston PhD ,&nbsp;Tonny Veenith PhD ,&nbsp;Richard J. Blanch PhD","doi":"10.1016/j.xops.2025.100890","DOIUrl":"10.1016/j.xops.2025.100890","url":null,"abstract":"<div><h3>Objective</h3><div>Assess retinal perfusion in sepsis, compared with uncomplicated postoperative care and healthy controls, and assess the effects of reduced perfusion on retinal structure and visual function.</div></div><div><h3>Design</h3><div>We conducted a prospective observational cohort study between March 2018 and December 2022, with follow-up measures collected 3 to 6 months after discharge.</div></div><div><h3>Subjects</h3><div>Twenty-four patients with sepsis were assessed in the intensive care unit (ICU) and 3 to 6 months later, 45 ICU control patients assessed during elective ICU admission after upper gastrointestinal cancer surgery, preoperatively, and 3 to 6 months later, and 15 healthy controls.</div></div><div><h3>Testing</h3><div>Assessments included retinal layer thickness using OCT, retinal perfusion using OCT angiography, and visual function using Humphrey visual field analysis. Organ dysfunction was assessed by Sequential Organ Failure Assessment (SOFA) scoring.</div></div><div><h3>Main Outcome Measures</h3><div>Superficial vascular plexus (SVP) retinal perfusion, OCT retinal ganglion cell layer (GCL) thickness, and mean deviation (MD) on Humphrey visual field testing were evaluated.</div></div><div><h3>Results</h3><div>Superficial vascular plexus retinal perfusion was 37.4% lower in patients with sepsis compared with ICU control patients (<em>P</em> &lt; 0.001) and 59.7% lower than in healthy controls, which returned to normal by final follow-up. Retinal perfusion correlated with the SOFA score (Pearson <em>r</em> = -0.57, <em>P</em> &lt; 0.001) and weakly correlated with C-reactive protein (<em>r</em> = -0.337, <em>P</em> = 0.01) and mean arterial pressure (<em>r</em> = 0.354, <em>P</em> = 0.006). In patients with sepsis and ICU controls, retinal perfusion in the ICU predicted subsequent GCL thickening, with every 1-unit decrease in SVP sum predicting a 1.88 μm increase in GCL thickness at follow-up (<em>P</em> = 0.003), and worsening visual field MD, with every 1-unit decrease in SVP sum predicting a 0.078 decibel lower MD (<em>P</em> = 0.023).</div></div><div><h3>Conclusions</h3><div>Retinal perfusion was impaired in patients with sepsis compared with both healthy controls and patients after major surgery. It was moderately associated with other measures of organ dysfunction assessed by SOFA. Reduced retinal perfusion in both patients with sepsis and patients after major surgery is strongly associated with subsequent GCL thickening and less strongly associated with decreased visual field MD, suggesting reduced retinal perfusion is associated with retinal damage, with consequent visual dysfunction.</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 100890"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097865","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":"Fuchs Endothelial Corneal Dystrophy Associations with Systemic Disease, Lifestyle, and Nutritional Intake","authors":"Myriam Böhm MD, MSc ,&nbsp;Aaron R. Kaufman MD ,&nbsp;Francesca Kahale MD ,&nbsp;Pia Leon MD ,&nbsp;Viridiana Kocaba MD, PhD ,&nbsp;Ula V. Jurkunas MD","doi":"10.1016/j.xops.2025.100899","DOIUrl":"10.1016/j.xops.2025.100899","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate associations between Fuchs endothelial corneal dystrophy (FECD) and systemic comorbidities, lifestyle factors, and dietary patterns, aiming to identify modifiable risk factors and inform therapeutic strategies.</div></div><div><h3>Design</h3><div>Case-control study integrating a cross-sectional survey with a retrospective chart review conducted at a tertiary referral center.</div></div><div><h3>Subjects</h3><div>The cohort included 100 individuals from the Cornea Service at Massachusetts Eye and Ear Infirmary: 50 patients with FECD and 50 age- and sex-matched controls within a 10-year range. Four controls were excluded due to protocol adherence.</div></div><div><h3>Methods</h3><div>Data collection involved chart reviews and a validated 152-item semiquantitative food frequency questionnaire. Smoking and exercise behaviors were assessed through structured questionnaires. Nutrient intake was adjusted for energy using the residual method. Thus, the energy-adjusted intake estimate is the residual from a regression model in which total energy intake is the independent variable and absolute nutrient intake is the dependent variable. Statistical comparisons included Wilcoxon rank-sum and Fisher exact tests (<em>P</em> &lt; 0.05).</div></div><div><h3>Main Outcome Measures</h3><div>Prevalence and statistical significance of systemic comorbidities, lifestyle behaviors, and dietary intake associated with FECD.</div></div><div><h3>Results</h3><div>Fuchs endothelial corneal dystrophy was associated with hyperlipidemia (74% vs. 50%, <em>P</em> = 0.023) and atrial fibrillation (26% vs. 8%, <em>P</em> = 0.031). Cumulative tobacco exposure was higher in patients with FECD (11.2 ± 15.1 vs. 6.1 ± 14.1 pack-years, <em>P</em> = 0.017). Patients with FECD had higher caloric intake (1862 ± 673 vs. 1463 ± 584 kcal, <em>P</em> = 0.027), reduced total fat (<em>P</em> = 0.036) and monounsaturated fat (<em>P</em> = 0.024), and increased sodium intake (<em>P</em> = 0.021). Elevated intake of zinc (<em>P</em> = 0.011), manganese (<em>P</em> = 0.043), and selenium (<em>P</em> = 0.007) was also observed.</div></div><div><h3>Conclusions</h3><div>Fuchs endothelial corneal dystrophy exhibits significant associations with cardiovascular comorbidities, cumulative tobacco exposure, and specific nutritional factors. The identified associations suggest possible directions for future intervention studies as on cardiovascular management, smoking cessation, and dietary modification. Further studies are warranted to explore mechanistic links and develop preventive and therapeutic strategies.</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 100899"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097862","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":"Corneal Cross-Linking Induces Increased Corneal Refractive Index, Which Generates Measurement Error of Central Corneal Thickness","authors":"Cynthia J. Roberts PhD ,&nbsp;Austin DeGroff OD ,&nbsp;Fernando M. Nuñez MD ,&nbsp;Andrew J. Hendershot MD ,&nbsp;Phillip T. Yuhas OD, PhD","doi":"10.1016/j.xops.2025.100904","DOIUrl":"10.1016/j.xops.2025.100904","url":null,"abstract":"<div><h3>Purpose</h3><div>This study investigated the impact of a higher-than-expected corneal index of refraction (n_c) on measured central corneal thickness (CCT) by Scheimpflug tomography and anterior-segment OCT.</div></div><div><h3>Design</h3><div>Theoretical analysis with prospective cohort study validation.</div></div><div><h3>Participants</h3><div>Twenty-four eyes from 23 participants met the criteria for inclusion in data analysis.</div></div><div><h3>Methods</h3><div>Two models were developed to represent side-view imaging with Scheimpflug geometry (model 1) and interferometric imaging in OCT (model 2). For both models, predicted CCT was calculated for various n_c values, and CCT measurement error was quantified. For validation, CCT was measured using Scheimpflug tomography and OCT in prospectively recruited subjects with keratoconus before and after corneal cross-linking (CXL). Central corneal thickness was compared between baseline and follow-up with paired t-test for each device and between devices using Wilcoxon signed rank tests for nonparametric data with significance threshold of <em>P</em> &lt; 0.05. Device-specific equations for CCT and n were solved iteratively at follow-up for those subjects with minimal difference in CCT at baseline to account for measurement error.</div></div><div><h3>Main Outcome Measures</h3><div>Central corneal thickness and n_c.</div></div><div><h3>Results</h3><div>In side-view model 1, a negative relationship between predicted CCT and n_c was found, as well as a negative association between CCT measurement error and n_c. OCT model 2 produced a positive association between predicted CCT and n_c and a positive association between CCT measurement error and n_c. As validation, CCT was stable (mean ± standard deviation ΔCCT = –0.57 ± 8.56 microns; <em>P</em> = 0.75, paired t-test) between the pre- and post-operative measurements made with OCT. However, CCT measured with Scheimpflug tomography was significantly lower after CXL than before it (–11.0 ± 11.3 microns; <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>The models indicate that an unknown increase in n_c after CXL results in underestimation of CCT from Scheimpflug-based devices and overestimation of CCT from OCT. The larger the difference in measured CCT between devices, the larger the increase in corneal refractive index that has occurred. Clinical validation aligns with both models, indicating the actual CCT is between those reported by each technology. Corneal cross-linking may alter the accuracy of diagnostic devices that rely on n_c to determine CCT.</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 100904"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097867","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":"In Vitro Stability and Preclinical Safety Evaluation of High-Dose Intravitreal Topotecan in Rabbits: Impact of Dose and Concentration","authors":"María J. Del Sole PhD ,&nbsp;Pablo Nejamkin PhD ,&nbsp;Javier Opezzo PhD ,&nbsp;Debora Chan PhD ,&nbsp;Andrés Farall PhD ,&nbsp;Gabriela Lamas MD ,&nbsp;Fabiana Lubieniecki MD ,&nbsp;David H. Abramson MD ,&nbsp;Paula Schaiquevich PhD","doi":"10.1016/j.xops.2025.100963","DOIUrl":"10.1016/j.xops.2025.100963","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the stability of concentrated solutions of topotecan and the ocular and systemic safety of administering repeated very high doses of intravitreal (IVi) topotecan in rabbits.</div></div><div><h3>Design</h3><div>Experimental study.</div></div><div><h3>Subjects</h3><div>Twenty four nontumor-bearing New Zealand White rabbits.</div></div><div><h3>Main Outcome Measures</h3><div>In vitro stability of topotecan solutions, hematologic parameters, fundoscopic examination, electroretinography (ERG) response, fundoscopic photography, and histologic assessment.</div></div><div><h3>Methods</h3><div>Three topotecan solutions (1-4 mg/ml) were assessed for stability at 4°C and –20°C for 1 month of drug reconstitution. Five groups of nontumor-bearing rabbits were used to evaluate systemic and ocular toxicity of 3 monthly doses of topotecan (50 μg, 100 μg, and 200 μg), injected in 50 μL or in 100 μL of diluent, or receiving only the vehicle. Ophthalmic, clinical, and electroretinographic evaluations were performed monthly. One month after the last injection, all eyes were enucleated for histological assessment. Electroretinographic parameters were compared among groups using a linear mixed-effects model (<em>P</em> &lt; 0.05).</div></div><div><h3>Results</h3><div>Topotecan solutions remained stable. During the study period, no hair loss, weight changes, or hematologic abnormalities were observed in any of the animal groups. Eyes treated with vehicle or injected with 3 doses of topotecan up to 100 μg per dose, delivered in either 50 μL or 100 μL diluent, showed no morphological, histological, or functional evidence of damage to the retina. However, eyes injected with 200 μg showed localized retinal alterations near the injection site on fundoscopy and histological analysis, and a significant decrease in the <em>a</em>- and <em>b</em>-wave amplitudes on ERG compared with the other groups (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>Three monthly IVi injections of topotecan 50 or 100 μg (100 μg and 200 μg human equivalent doses) caused no systemic or ocular toxicity in a nontumor-bearing rabbit model. Repeated 200 μg doses (400 μg human-equivalent dose) resulted in localized retinal morphological alterations and small but detectable changes in electrophysiological parameters. The results of this study may have clinical utility in the assessment of very high-dose topotecan as a salvage treatment of highly compromised eyes with recurrent or relapsed subretinal seeds and retinal tumors.</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 1","pages":"Article 100963"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519796","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":"Safety and Efficacy of Orally Administered SJP-0008 in Central Retinal Artery Occlusion: A Phase IIa Randomized Clinical Trial","authors":"Satoru Tsuda MD, PhD ,&nbsp;Hiroshi Kunikata MD, PhD ,&nbsp;Kazuki Hashimoto MD, PhD ,&nbsp;Toshifumi Asano MD, PhD ,&nbsp;Azusa Ito MD, PhD ,&nbsp;Mitsuhide Yoshida DDS, PhD ,&nbsp;Masayuki Yasuda MD, PhD ,&nbsp;Fumihiko Nitta MD, PhD ,&nbsp;Toru Nakazawa MD, PhD","doi":"10.1016/j.xops.2025.100965","DOIUrl":"10.1016/j.xops.2025.100965","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the efficacy and safety of orally administered calpain inhibitor SJP-0008 in Japanese patients with central retinal artery occlusion (CRAO), to establish a disease registry for the prospective tracking of observational data from patients with CRAO, intended for regulatory use, and to support the development of new therapeutic agents for CRAO.</div></div><div><h3>Design</h3><div>This was a 2-part study. Part 1 was a physician-/investigator-initiated, phase IIa, single-center, randomized, double-blinded, parallel-group study. Part 2 was a prospective cohort study, during which the CRAO registry was established, and included patients diagnosed with CRAO (including a nonrandomized registry cohort, the non-SJP group, which did not receive SJP-0008). Additionally, in part 2, a combined analysis was performed using data from part 1 patients.</div></div><div><h3>Participants</h3><div>The study participants were patients recruited within 48 hours of developing CRAO.</div></div><div><h3>Methods</h3><div>SJP-0008 administration was initiated at least 3 hours but no more than 48 hours after the onset of CRAO. Patients were randomized in a 1:1 ratio using masked randomization to receive either 100-mg or 200-mg doses of SJP-0008. The dosing period was defined as the 4-week postinitiation period (up to 29 days), followed by an 8-week postobservation phase.</div></div><div><h3>Main Outcome Measures</h3><div>The main outcome measure was to determine the efficacy of SJP-0008 treatment; the primary endpoint was the change in ETDRS visual acuity at 12 weeks in the target eye of patients with CRAO.</div></div><div><h3>Results</h3><div>The study included 28 patients (mean age: 68.8 ± 14.9 years; 78.6% male). ETDRS scores (mean [95% confidence interval]) were higher at week 12 than at baseline in both the 100-mg (27.9 letters [10.14, 45.61]) and 200-mg (25.7 letters [12.02, 39.40]) SJP-0008 groups, in contrast to the non-SJP group (10.2 letters [4.58, 15.76]). The improvement in the 200-mg SJP-0008 group was greater than in the nonrandomized non-SJP group (<em>P</em> = 0.040). No safety concerns were identified.</div></div><div><h3>Conclusions</h3><div>The preliminary study supports the safety and efficacy of oral administration of SJP-0008 for treating CRAO, with greater improvement compared with the nonrandomized registry cohort. However, large-scale, multicenter randomized controlled trials are warranted to validate the findings of this study.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100965"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Patients at High Risk of Lapses in Diabetic Retinopathy Care: A Machine Learning Study","authors":"Jizhou Tian MS ,&nbsp;Diep Tran MS ,&nbsp;Zainab Rustam MBBS ,&nbsp;Gina Zhu BS ,&nbsp;Paul Nagy PhD ,&nbsp;Hadi Kharrazi MD, PhD ,&nbsp;Deidra C. Crews MD, ScM ,&nbsp;Zitong Wang PhD ,&nbsp;Scott L. Zeger PhD ,&nbsp;Cindy X. Cai MD, MS","doi":"10.1016/j.xops.2025.100967","DOIUrl":"10.1016/j.xops.2025.100967","url":null,"abstract":"<div><h3>Objective</h3><div>To predict lapses in diabetic retinopathy (DR) care.</div></div><div><h3>Design</h3><div>Retrospective cohort study.</div></div><div><h3>Subjects</h3><div>Adults ≥18 years with diabetes seen at the Wilmer Eye Institute for DR screening or treatment between 2012 and 2022.</div></div><div><h3>Main Outcome Measures</h3><div>Whether an office visit for DR screening or treatment was followed by a lapse in care.</div></div><div><h3>Methods</h3><div>Three versions of prediction algorithms were constructed using random forests (RFs). XGBoost (XGB) was used as a confirmatory analysis. Random forest-A and XGB-A included electronic health record (EHR) variables alone (e.g., sociodemographic, insurance, ophthalmic diagnoses, lead time, and recommended follow-up time). Random forest-B and XGB-B added location-based social determinants of health (SDoH) variables (e.g., Area Deprivation Index). Random forest-C and XGB-C added history of lapses in care (e.g., whether the patient has ever had lapses in care before). The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) were calculated for each algorithm.</div></div><div><h3>Results</h3><div>A total of 36 995 patients (mean age 62 years, 53% female, 47% non-Hispanic White, 38% non-Hispanic Black, and 4% Hispanic) and 141 930 office visits were included. The best performing model was RF-C with an AUROC of 0.774 (0.772–0.776) and AUPRC of 0.707 (0.704–0.711), outperforming RF-A and RF-B in AUROC and AUPRC (<em>P</em> &lt; 0.001 for each comparison). XGB-C similarly outperformed XGB-A and XGB-B (<em>P</em> &lt; 0.001 for each comparison).</div></div><div><h3>Conclusions</h3><div>We developed RF algorithms, as well as XGB confirmatory models, to predict whether patients with diabetes will experience a lapse in DR care. The best prediction was achieved using EHR variables, location-based SDoH variables, and history of lapses in care. These models offer the opportunity to identify high-risk patients and offer additional resources to reduce lapses in care and potentially vision loss from DR.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100967"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association of Lapses in Diabetic Retinopathy Care with Vision Impairment","authors":"Gina Zhu BS ,&nbsp;Erik Westlund PhD ,&nbsp;Diep Tran MS ,&nbsp;Cindy X. Cai MD, MS","doi":"10.1016/j.xops.2025.100958","DOIUrl":"10.1016/j.xops.2025.100958","url":null,"abstract":"<div><h3>Objective</h3><div>To identify the association of lapses in diabetic retinopathy (DR) care with vision impairment among patients with type 2 diabetes (T2D), stratified by DR severity and treatment status.</div></div><div><h3>Design</h3><div>Retrospective cohort study.</div></div><div><h3>Subjects</h3><div>Adults with T2D seen at the Wilmer Eye Institute from 2013 to 2023.</div></div><div><h3>Methods</h3><div>Propensity score modeling was used to estimate the probability that a patient would experience a lapse in care during a 2-year observation window based on sociodemographic (age, sex, self-reported race or ethnicity, insurance), ocular (baseline visual acuity, ophthalmic comorbidities, history of retinal treatments), and medical factors (Diabetes Complication Severity Index, Charlson Comorbidity Index). Doubly robust logistic regression models using inverse probability weighting of the propensity scores were used to estimate the association of care lapses with vision impairment. We also estimated average marginal effects to examine the probability difference in vision impairment associated with care lapses among patients grouped by DR severity (no DR, nonproliferative DR, proliferative DR) and treatment status (no treatment, any treatment, anti-VEGF only, panretinal photocoagulation only).</div></div><div><h3>Main Outcome Measures</h3><div>Vision impairment (or vision worse than Snellen equivalent 20/40) at the end of the observation period.</div></div><div><h3>Results</h3><div>A total of 45 764 patients with 90 440 eyes contributed to the study. Most patients were female (52%), and the average age was 61.7 years. A total of 81% had a lapse in care. Patients who had a lapse in care had 50% higher odds of having vision impairment compared with patients who never lapsed (<em>P &lt;</em> 0.001). This association was seen across all subgroups of DR severity and treatment status (all <em>P &lt;</em> 0.001).</div></div><div><h3>Conclusions</h3><div>For patients with T2D, a lapse in care was associated with higher odds of having vision impairment, regardless of underlying severity of DR or treatment status. These findings highlight the importance of longitudinal DR care and reducing lapses in care to prevent vision loss.</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 100958"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466349","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":"Lipidome's Role in Diabetic Retinopathy Subtypes via Inflammation: Mendelian Randomization and Mediation Analysis","authors":"Xiaotong Xu MD, MB ,&nbsp;Nianen Liu MM, MB ,&nbsp;Kaixuan Dong MD, MB ,&nbsp;Shuai Ouyang MD, MB ,&nbsp;Weihong Yu MD, PhD","doi":"10.1016/j.xops.2025.100951","DOIUrl":"10.1016/j.xops.2025.100951","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to explore the causal relationships between plasma lipidome, inflammatory cytokines, and diabetic retinopathy (DR) subtypes using a two-sample Mendelian randomization (MR) approach and mediation analysis.</div></div><div><h3>Design</h3><div>Mendelian randomization study and mediation analysis.</div></div><div><h3>Subjects</h3><div>Genome-wide association study (GWAS) data of 179 plasma lipid species and 91 inflammatory cytokines from the public GWAS database. Genome-wide association study data of DR and its subtypes from the FinnGen consortium.</div></div><div><h3>Methods</h3><div>Primary causal estimates were derived via inverse-variance weighted method, complemented by 4 sensitivity methods (weighted median, MR-Egger, simple mode, weighted mode). Mediation analysis was performed to determine the extent to which inflammatory cytokines mediate the effects of lipid species on DR subtypes. The Cochran Q-test, MR-Egger intercept test, and leave-one-out were used for sensitivity analyses. Mendelian randomization-Egger regression and Mendelian Randomization Pleiotropy RESidual Sum and Outlier were used to detect potential directional pleiotropy. We employed a two-sample MR analysis to assess the causal effects of specific lipid species on the risk of DR and its subtypes. Genome-wide association study summary statistics for lipid species and inflammatory cytokines were used. Mediation analysis was performed to determine the extent to which inflammatory cytokines mediate the effects of lipid species on DR subtypes.</div></div><div><h3>Main Outcome Measures</h3><div>Genetic causal associations between lipid species, inflammatory cytokines, and DR subtypes.</div></div><div><h3>Results</h3><div>Mendelian randomization analyses showed that most of the identified plasma lipids were significantly protective against DR and its subtypes, mainly belonging to the phosphatidylcholine and phosphatidylethanolamine classes. Triacylglycerols have different roles in different severities of DR, and inflammatory cytokines had different causal effects on DR and its subtypes. Mediation analyses identified 10 specific inflammatory cytokine–mediated pathways of lipid species on DR, of which 7 had about 10% of the mediating effect, with inflammatory cytokines in the remaining 3 playing mediating effects opposite to the pathways.</div></div><div><h3>Conclusions</h3><div>This study highlights the complex interplay between lipid metabolism and inflammation in the pathogenesis of DR. Specific lipid species protect against DR, with inflammatory cytokines mediating these effects, suggesting potential therapeutic targets for DR management.</div></div><div><h3>Financial Disclosure(s)</h3><div>The author 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 100951"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466350","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}