Cynthia J. Roberts PhD , Austin DeGroff OD , Fernando M. Nuñez MD , Andrew J. Hendershot MD , Phillip T. Yuhas OD, PhD
{"title":"Corneal Cross-Linking Induces Increased Corneal Refractive Index, Which Generates Measurement Error of Central Corneal Thickness","authors":"Cynthia J. Roberts PhD , Austin DeGroff OD , Fernando M. Nuñez MD , Andrew J. Hendershot MD , 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<sub>c</sub>) 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<sub>c</sub> 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> < 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<sub>c.</sub></div></div><div><h3>Results</h3><div>In side-view model 1, a negative relationship between predicted CCT and n<sub>c</sub> was found, as well as a negative association between CCT measurement error and n<sub>c</sub>. OCT model 2 produced a positive association between predicted CCT and n<sub>c</sub> and a positive association between CCT measurement error and n<sub>c</sub>. 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> < 0.001).</div></div><div><h3>Conclusions</h3><div>The models indicate that an unknown increase in n<sub>c</sub> 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<sub>c</sub> 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":"2025-08-05","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":"Validation of an Artificial Intelligence–Based Anterior Chamber Depth Estimation Using a Smartphone-Compatible Slit Lamp Device","authors":"Takahiro Mizukami MD , Eisuke Shimizu MD, PhD , Kenta Tanaka BEng , Hiroki Nishimura BOpt, MPH , Shintaro Nakayama LLB , Ryota Yokoiwa BEng , Satoru Ueno MD, PhD , Soichiro Mishima MD , Yoshikazu Shimomura MD, PhD","doi":"10.1016/j.xops.2025.100906","DOIUrl":"10.1016/j.xops.2025.100906","url":null,"abstract":"<div><h3>Purpose</h3><div>Accurate evaluation of anterior chamber depth (ACD), a major risk factor for angle closure, is clinically important. Although standard techniques provide reliable measurements, they are often labor-intensive, technically demanding, and time-consuming. To address this, we previously developed an artificial intelligence (AI) algorithm capable of estimating ACD from slit lamp photographs. This study sought to assess the performance of this AI model when applied via the Smart Eye Camera (SEC), a smartphone-compatible slit lamp imaging system, by comparing its estimates to those obtained with anterior segment OCT (AS-OCT) at a separate institution.</div></div><div><h3>Design</h3><div>An evaluation of diagnostic test.</div></div><div><h3>Participants</h3><div>Five hundred fifty-six phakic eyes (268 nondilated and 288 dilated eyes) from 329 Asian patients.</div></div><div><h3>Methods</h3><div>A retrospective analysis was performed on images captured using both the SEC and AS-OCT. Anterior chamber depth values generated by the AI model embedded in the SEC were compared with corresponding measurements obtained using AS-OCT.</div></div><div><h3>Main Outcome Measures</h3><div>Metrics, including mean absolute error (MAE), mean squared error (MSE), Pearson correlation coefficient, and the intraclass correlation coefficient (ICC), were calculated to evaluate model performance.</div></div><div><h3>Results</h3><div>The AI algorithm integrated into the SEC demonstrated the capability to estimate the ACD with an MAE of 0.119 ± 0.0949 mm and an MSE of 0.0233 ± 0.0557 mm. A strong correlation was observed between ACD measurements obtained using AS-OCT and those estimated by AI (<em>R</em> = 0.922; 95% confidence interval, 0.908–0.933). The ICC for agreement between AI-estimated and AS-OCT-measured ACD was 0.903, indicating excellent reliability.</div></div><div><h3>Conclusions</h3><div>Our AI model, embedded within the SEC platform, demonstrated high accuracy in estimating ACD when benchmarked against AS-OCT. Given its portability and user-friendliness, the SEC presents a promising option for accessible ACD screening across diverse clinical environments.</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 100906"},"PeriodicalIF":4.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097866","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":"Caffeine Therapy Reduces Severe Retinopathy of Prematurity in Neonates with Gestational Age between 23 and 28 Weeks","authors":"Yuki Otsuka MD, PhD, Futoshi Taketani MD, PhD, Miou Hirose MD, Hideyasu Oh MD, PhD","doi":"10.1016/j.xops.2025.100903","DOIUrl":"10.1016/j.xops.2025.100903","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the association of caffeine citrate therapy with the onset and exacerbation of retinopathy of prematurity (ROP).</div></div><div><h3>Design</h3><div>A retrospective observational cohort study.</div></div><div><h3>Participants</h3><div>Preterm neonates born at Hyogo Prefectural Amagasaki General Medical Center between January 2018 and December 2023 were included.</div></div><div><h3>Methods</h3><div>Data on maternal (age; comorbid hypertensive disorders of pregnancy and gestational diabetes mellitus; fetal growth restriction; and cesarean section) and neonatal (sex; gestational age; birth weight; zone at initial examination; Apgar scores; respiratory distress syndrome; chronic lung disease; tracheal intubation; duration of tracheal intubation; duration of oxygen therapy; and caffeine therapy) risk factors for ROP were collected from medical records.</div></div><div><h3>Main Outcome Measures</h3><div>Retinopathy of prematurity onset and severe ROP were defined as stage ≥1 and stage ≥3 during the course of follow-up, respectively. The association between caffeine therapy and the onset of any ROP and severe ROP was investigated.</div></div><div><h3>Results</h3><div>Among 202 neonates included in the current study, 94 (46.5%) developed any ROP (stage ≥1) during the observational period. Only the zone at initial examination affected the onset of any ROP (<em>P</em> < 0.01). However, in 115 neonates born at <32 weeks gestational age and with <1500 g birth weight, larger zones at baseline and caffeine treatment were associated with decreased severe ROP (<em>P</em> = 0.017 and <em>P</em> < 0.01, respectively). Additionally, in 54 neonates with gestational age between 23 and 28 weeks, only caffeine therapy was associated with decreased development of severe ROP (<em>P</em> < 0.01). All 4 neonates with gestational age <23 weeks progressed to severe ROP despite caffeine therapy.</div></div><div><h3>Conclusions</h3><div>Caffeine therapy may be a potential treatment strategy to prevent the progression of severe ROP in neonates born between 23 and 28 weeks' gestational age.</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 100903"},"PeriodicalIF":4.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097864","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}
Susanna S. Park MD, PhD , Jennifer McCormack MS , Dagmar Salazar MS , Jacquie S. King MS , Marisa Salvador BA , Gerhard Bauer BS , Brian Fury MS , Mehrdad Abedi MD , Ala Moshiri MD, PhD , Denise Macias BS , Kareem Moussa MD , Radhika Kondapaka MBBS , Robert Lindblad MD , Rasmus Hoeg MD , Jan A. Nolta PhD
{"title":"Randomized Study of Intravitreal Autologous CD34+ Stem Cells in Central Retinal Vein Occlusion (Treatment of Retinal vein occlusion Using STem cells [TRUST] Report 1): Safety and Feasibility","authors":"Susanna S. Park MD, PhD , Jennifer McCormack MS , Dagmar Salazar MS , Jacquie S. King MS , Marisa Salvador BA , Gerhard Bauer BS , Brian Fury MS , Mehrdad Abedi MD , Ala Moshiri MD, PhD , Denise Macias BS , Kareem Moussa MD , Radhika Kondapaka MBBS , Robert Lindblad MD , Rasmus Hoeg MD , Jan A. Nolta PhD","doi":"10.1016/j.xops.2025.100905","DOIUrl":"10.1016/j.xops.2025.100905","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the safety and feasibility of intravitreal injection of autologous CD34+ bone marrow stem cells (BMSCs) in eyes with vision loss from central retinal vein occlusion (CRVO).</div></div><div><h3>Design</h3><div>Phase I/II single-center, prospective, randomized, sham-controlled, double-masked study.</div></div><div><h3>Participants</h3><div>Participants with CRVO of 6 to 42 months duration, best-corrected visual acuity (VA) of 20/40 to 20/400, and no concurrent retinopathy or optic neuropathy contributing to vision loss in the study eye. The exclusion criteria include any concurrent systemic condition that would alter bone marrow components.</div></div><div><h3>Methods</h3><div>Participants were randomized to immediate cell injection followed by sham injection at month 6 or immediate sham injection followed by cell injection at month 6. Cell injection consisted of a bone marrow aspiration and intravitreal injection of autologous CD34+ BMSCs. CD34+ BMSCs were isolated from the mononuclear cell fraction of bone marrow using Miltenyi CliniMACS system under current good manufacturing practices. Isolated cells were released for intravitreal injection if they passed the release criteria for quantity, sterility, and viability accepted by the US Food and Drug Administration. Sham injection consisted of a sham bone marrow aspiration and intravitreal injection without entering bone or eye. Eye examination, microperimetry, fundus photography, fluorescein angiography, electroretinography, OCT, and OCT angiography were performed at baseline and during study follow-up of 12 months.</div></div><div><h3>Main Outcome Measures</h3><div>Adverse events (AEs) associated with study treatment, number of CD34+ BMSCs injected intravitreally.</div></div><div><h3>Results</h3><div>Sixteen participants (16 eyes) were randomized to 1 of 2 study groups. All received intravitreal injection of autologous CD34+ BMSCs (mean 4.3 million cells) and completed the study follow-up. Rubeosis with vitreous hemorrhage occurred in 1 study eye, <1 month after sham injection and 7 months after cell injection, attributed to normal progression of CRVO. There were no other serious ocular AEs. The most common AE related to the study cell injection was new floaters (15/16, 93%). Other ocular AEs were similarly noted after sham injection. No eye had persistent VA loss of ≥15 letters after cell injection.</div></div><div><h3>Conclusions</h3><div>Intravitreal injection of autologous CD34+ BMSCs appears well-tolerated and feasible in eyes with vision loss from CRVO.</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 100905"},"PeriodicalIF":4.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050609","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 Choroidal Vascular Hyperpermeability and Vortex Vein Anastomoses in Central Serous Chorioretinopathy","authors":"Yasunori Miyara MD, Nobuhiro Terao MD, PhD, Naoya Imanaga MD, PhD, Hideki Koizumi MD, PhD","doi":"10.1016/j.xops.2025.100901","DOIUrl":"10.1016/j.xops.2025.100901","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the association between choroidal vascular hyperpermeability (CVH) and vortex vein anastomoses in the macula of patients with central serous chorioretinopathy (CSC).</div></div><div><h3>Design</h3><div>A retrospective comparative study.</div></div><div><h3>Subjects</h3><div>A total of 118 eyes of 106 patients with CSC.</div></div><div><h3>Methods</h3><div>All patients underwent choroidal en face imaging using widefield swept-source OCT. The eyes were classified into watershed zone (WZ) and non-WZ groups. The horizontal WZ through the macula was identified in the WZ group, whereas it was ill-defined in the non-WZ group, because of marked anastomoses between the superior and inferior vortex veins. The number and distribution of CVH areas, as detected on indocyanine green angiography, were evaluated and compared between the 2 groups.</div></div><div><h3>Main Outcome Measures</h3><div>Association between CVH and vortex vein anastomoses in CSC.</div></div><div><h3>Results</h3><div>Overall, 118 eyes were classified into the WZ (n = 81) and non-WZ (n = 37) groups. The mean number of CVH areas per eye was significantly higher in the non-WZ group than in the WZ group (4.95 vs. 2.43; <em>P</em> < 0.001). In both groups, almost half of the CVH areas were located in proximity to the boundary between the superior and inferior vortex veins. However, CVH areas outside the retinal vascular arcade were more frequently observed in the non-WZ group than in the WZ group (31.1% vs. 18.8%; <em>P</em> = 0.002). Among 95 eyes with asymmetric vortex veins, CVH areas on the nondominant vortex vein side were more frequently observed in the non-WZ group than in the WZ group (29.7% vs. 18.1%; <em>P</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>Central serous chorioretinopathy eyes with an ill-defined WZ due to marked vortex vein anastomoses had more multifocal and extensive CVH areas than those with an identified WZ. The presence of vortex vein anastomoses may affect the number and distribution of CVH areas in eyes with CSC.</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 100901"},"PeriodicalIF":4.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097863","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}
Myriam Böhm MD, MSc , Aaron R. Kaufman MD , Francesca Kahale MD , Pia Leon MD , Viridiana Kocaba MD, PhD , Ula V. Jurkunas MD
{"title":"Fuchs Endothelial Corneal Dystrophy Associations with Systemic Disease, Lifestyle, and Nutritional Intake","authors":"Myriam Böhm MD, MSc , Aaron R. Kaufman MD , Francesca Kahale MD , Pia Leon MD , Viridiana Kocaba MD, PhD , 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> < 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":"2025-07-31","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}
JeongGoo Lee PhD, Sun Young Lee MD, PhD, Dimitrios Pollalis MD, Martin Heur MD, PhD
{"title":"Small Extracellular Vesicle–Mediated Peptide Delivery to the Mouse Corneal Endothelium In Vivo","authors":"JeongGoo Lee PhD, Sun Young Lee MD, PhD, Dimitrios Pollalis MD, Martin Heur MD, PhD","doi":"10.1016/j.xops.2025.100900","DOIUrl":"10.1016/j.xops.2025.100900","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the utility of human corneal endothelial cell (hCEC)-derived small extracellular vesicles (sEVs) as a delivery system to the mouse corneal endothelium (CE) in vivo.</div></div><div><h3>Design</h3><div>Laboratory study.</div></div><div><h3>Subjects</h3><div>C57BL/6 mice.</div></div><div><h3>Methods</h3><div>hCEC-derived sEV were isolated from culture media using differential ultracentrifugation. Size, number, and morphology were characterized using nanoparticle tracking analysis and transmission electron microscopy (TEM). sEV markers were confirmed using an sEV detection antibody panel. PKH26-labeled sEV were injected into the anterior chamber of wild-type mice, and corneal endothelial uptake of sEV was assessed by colocalization of 4′,6-diamidino-2-phenylindole and PKH26 fluorescence on corneal whole mounts. Saponin permeabilization and sonication were used to load FITC-conjugated peptide into sEV. Delivery to mouse CE in vivo following intracameral injection was assessed by colocalization analysis of PKH26-labeled sEV with FITC-conjugated peptide. An average of 5 × 10<sup>8</sup> to 1 × 10<sup>9</sup> particles/plate with a peak size of 120 nm sEV were isolated.</div></div><div><h3>Main Outcome Measures</h3><div>sEV-mediated endothelial targeting.</div></div><div><h3>Results</h3><div>Morphology and size of sEVs were confirmed by TEM, and the presence of sEV markers, flotillin-1, ICAM, programmed cell death 6 interacting protein (ALIX), immunoglobulin superfamily member 8 (CD81), lysosome-associated membrane protein 3 (CD63), annexin A5, and tumor susceptibility gene 101 (TSG101), was confirmed by immunoblotting. Confocal microscopy of whole-mounted mouse corneas, performed 2 days after intracameral injection of PKH26-labeled sEVs containing FITC-conjugated peptide, showed localization of sEVs within the CE. Colocalization of PKH26 and FITC signals in the mouse CE confirmed delivery of the peptide cargo via hCEC-derived sEVs in the mouse CE in vivo.</div></div><div><h3>Conclusions</h3><div>We demonstrate proof of principle of using hCEC-derived sEVs for delivery of potential therapeutic agents to the mouse CE in vivo via intracameral injection.</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 100900"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109419","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":"Seasonal Variations of Vogt-Koyanagi-Harada Disease in Japan: A Study on Long-Term Trends and the Influence of Coronavirus Disease 2019 (COVID-19)","authors":"Yuki Mizuki MD, PhD , Akira Meguro PhD , Koji Yamamoto PhD , Tatsukata Kawagoe MD, PhD , Nobuyuki Horita MD, PhD , Hiroyuki Okada MD, PhD , Norihiro Yamada MD, PhD , Takuto Sakono MD, PhD , Mami Ishihara MD, PhD , Shigeaki Ohno MD, PhD , Nobuhisa Mizuki MD, PhD","doi":"10.1016/j.xops.2025.100902","DOIUrl":"10.1016/j.xops.2025.100902","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate seasonal trends in the onset of Vogt-Koyanagi-Harada (VKH) disease in Japan and evaluate the influence of the coronavirus disease 2019 (COVID-19) pandemic, including severe cases and vaccination campaigns, on disease onset.</div></div><div><h3>Design</h3><div>A retrospective cohort study using clinical records and public health data.</div></div><div><h3>Participants</h3><div>A total of 320 Japanese VKH patients with a known month of onset who were initially treated at Yokohama City University Hospital between April 2007 and March 2024.</div></div><div><h3>Methods</h3><div>The monthly distribution of VKH onset cases was assessed using the Roger test to determine seasonality before and after the COVID-19 pandemic. Severe COVID-19 case data (April 2020 to March 2024) were obtained from government sources. The COVID-19 vaccine administration data (April 2021 to March 2024) were collected from a major local clinic. Multiple linear regression was used to evaluate the temporal relationship between VKH onset and severe COVID-19 cases or vaccination, incorporating current-month (lag0), 1-month lag (lag1), and 2-month lag (lag2) predictors.</div></div><div><h3>Main Outcome Measures</h3><div>Monthly number of VKH onset cases, seasonal trends, and statistical associations with COVID-19-related variables.</div></div><div><h3>Results</h3><div>Seasonal variation was significant in VKH onset both before (<em>P</em> = 0.02) and after (<em>P</em> < 0.001) the pandemic, with a shift in peak onset from spring to late summer/fall. Vogt-Koyanagi-Harada onset was significantly associated with severe COVID-19 cases in the current month (β = 0.097; <em>P</em> = 0.02) and with COVID-19 vaccination counts with a 1-month delay (β = 0.83; <em>P</em> = 0.002). The regression models showed moderate to strong explanatory power (adjusted <em>R</em><sup><em>2</em></sup> = 0.52 and 0.80, respectively).</div></div><div><h3>Conclusions</h3><div>This study revealed a postpandemic shift in the seasonal distribution of VKH onset in Japan, with peaks aligning with increased severe COVID-19 infections in the current month and vaccination activity in the preceding month. The findings suggest that both acute viral immune responses and delayed vaccine-induced immunity may contribute to VKH onset, highlighting the need for further investigation into the immunological mechanisms linking COVID-19 and autoimmune disease expression.</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 100902"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109418","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 Impact of Pharmacological Pupil Dilation on Anterior Chamber Cells Counting Using OCT","authors":"Priscilla Manni MD , Francesco Romano MD , Matteo Airaldi MD , Chiara Zaffalon MD , Lucrezia Barbieri MD , Federico Zicarelli MD , Marta Oldani MD , Domenico Chisari MD , Luca Cimino MD , Alessandro Invernizzi MD","doi":"10.1016/j.xops.2025.100896","DOIUrl":"10.1016/j.xops.2025.100896","url":null,"abstract":"<div><h3>Purpose</h3><div>Anterior chamber (AC) cells are seen as hyperreflective dots (HRDs) on anterior segment OCT (AS-OCT), but many factors can affect their objective counting. The aim of this study was to evaluate the effect of pharmacological dilation with tropicamide 0.5% (T) or phenylephrine 2.5% + tropicamide 0.5% (PH + T) on the assessment of AC HRDs density measured in healthy eyes by AS-OCT.</div></div><div><h3>Design</h3><div>Cross-sectional, observational study.</div></div><div><h3>Participants</h3><div>Healthy subjects with no history of uveitis, no ocular or systemic conditions, and no recent ocular surgery.</div></div><div><h3>Methods</h3><div>Participants underwent comprehensive ophthalmic examinations, including single-line AS-OCT (16.5 mm; μm:pixel ratio = 8.79; Anterion, Heidelberg Engineering) imaging before (miosis) and after pupil dilation with either T or PH + T drops. Hyperreflective dots were quantified using FIJI (National Institutes of Health, Bethesda) through the Analyze Particles tool after image binarization. Hyperreflective dot density was calculated by dividing the total HRDs by the AC area and expressed as the number per 10 000 pixels². Iris displacement after dilation was measured using the apex-to-pupil distance (APD).</div></div><div><h3>Main Outcome Measures</h3><div>Anterior chamber HRDs density before and after dilation measured by AS-OCT. A generalized Poisson mixed-effects model was used to evaluate the effects of group (miosis, T, PH + T), lens status (phakic, pseudophakic), and their interaction on HRD density. Covariates included age, sex, iris color, and variation in APD after dilation (APDD).</div></div><div><h3>Results</h3><div>A total of 100 eyes from 59 healthy participants (55.9% female), mean age 73.0 ± 11.7 years were included. Mean (standard deviation) HRDs density (per 10 000 pixels²) significantly increased from 0.79 (1.44) in normal photopic conditions to 1.71 (3.30) after the dilatation in the T group and from 0.52 (0.83) to 15.8 (25.8) in the PH + T group (<em>P</em> < 0.001). Dilation with T (<em>P</em> = 0.03) or PH + T (<em>P</em> < 0.001), increased APDD (<em>P</em> < 0.001), and the interaction between PH + T and phakic status (<em>P</em> < 0.001) were all significantly associated with higher HRDs density.</div></div><div><h3>Conclusions</h3><div>Pharmacological dilation, especially with PH + T, significantly increases HRDs in the AC of healthy subjects, with a more pronounced effect in phakic eyes and greater APDD. These findings suggest increased iris-lens friction and potential pigment release after dilation, providing critical considerations for standardizing AS-OCT-based assessments of AC inflammation.</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 100896"},"PeriodicalIF":4.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159816","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}
Asmaa A. Zidan MD , Elsayed Elbasiony MD, MSc , Zhirong Lin PhD , Sheyda Najafi PhD , Kathryn Pate PhD , Jia Yin MD, PhD
{"title":"Supersaturated Oxygen Emulsion Mitigates Hypoxia-Driven Corneal Neovascularization after Alkali Burn","authors":"Asmaa A. Zidan MD , Elsayed Elbasiony MD, MSc , Zhirong Lin PhD , Sheyda Najafi PhD , Kathryn Pate PhD , Jia Yin MD, PhD","doi":"10.1016/j.xops.2025.100898","DOIUrl":"10.1016/j.xops.2025.100898","url":null,"abstract":"<div><h3>Purpose</h3><div>Alkali burn is a vision-threatening ocular emergency with no targeted acute therapy. We previously identified tissue hypoxia as a key driver and developed a perfluorodecalin-based supersaturated oxygen emulsion (SSOE) that delivers high levels of oxygen topically. In this study, we aim to investigate the role of hypoxia-inducible factor signaling in postburn sequalae and evaluate the therapeutic efficacy and timing of SSOE in treating ocular alkali burn.</div></div><div><h3>Design</h3><div>Experimental animal study.</div></div><div><h3>Subjects</h3><div>A total of 207 BALB/c mice were used in this study. Subjects were assigned to 6 experimental groups: naïve (n = 31), untreated or vehicle-treated controls (n = 75), and treatment groups receiving SSOE either immediately postinjury (n = 33), or with delayed initiation at 1 day (n = 26), 2 days (n = 21), or 5 days (n = 21) after alkali burn. Where possible, mice were used for multiple outcome assessments to reduce total animal use in accordance with ethical and institutional guidelines.</div></div><div><h3>Methods</h3><div>Alkali burn was induced by applying 1M sodium hydroxide solution to the central cornea of BALB/c mice, followed by immediate or delayed (by 1, 2, or 5 days) topical application of SSOE or vehicle control daily for 14 days. Corneal opacity, neovascularization (NV), and cataract formation were assessed, and hypoxia-inducible factor 1-alpha (HIF-1α) and VEGF expression were measured.</div></div><div><h3>Main Outcome Measures</h3><div>Corneal NV, anterior chamber (AC) inflammation, cataract formation, and HIF-1α or VEGF expression.</div></div><div><h3>Results</h3><div>Alkali burn led to persistent HIF-1α activation in the cornea up to day 14 postinjury, which was strongly correlated with corneal NV. Immediate SSOE treatment significantly reduced corneal NV, edema, AC inflammation, cataract formation, and expression of HIF-1α and VEGF at days 14 and 28. Delayed SSOE application (up to 5 days postinjury) also improved corneal NV, edema, inflammation, and fibrosis but did not prevent cataract formation.</div></div><div><h3>Conclusions</h3><div>Daily SSOE treatment mitigates hypoxia-driven corneal NV by inhibiting HIF-1α and VEGF signaling. Early administration offers the greatest benefit, though delayed treatment remains effective in reducing corneal damage. These findings support the potential of SSOE as a novel topical therapy for chemical eye injuries.</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":"5 6","pages":"Article 100898"},"PeriodicalIF":4.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913275","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}