Investigative ophthalmology & visual science最新文献

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Optimizing Subretinal Bleb Formation for Visual Streak Involvement in a Porcine Model for Retinal Gene Therapy. 在猪视网膜基因治疗模型中优化视网膜下出血点的形成,以实现视觉条纹参与。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.41
Immanuel P Seitz, Tobias Peters, Felix Reichel, Andrea Bähr, Hanna Auch, Jan Motlik, Taras Ardan, Jana Juhasova, Yaroslav Nemesh, Stefan Juhás, Nikolai Klymiuk, Manuel Dominik Fischer
{"title":"Optimizing Subretinal Bleb Formation for Visual Streak Involvement in a Porcine Model for Retinal Gene Therapy.","authors":"Immanuel P Seitz, Tobias Peters, Felix Reichel, Andrea Bähr, Hanna Auch, Jan Motlik, Taras Ardan, Jana Juhasova, Yaroslav Nemesh, Stefan Juhás, Nikolai Klymiuk, Manuel Dominik Fischer","doi":"10.1167/iovs.65.12.41","DOIUrl":"10.1167/iovs.65.12.41","url":null,"abstract":"<p><strong>Purpose: </strong>Subretinal (SR) injection in porcine models is a promising avenue for preclinical evaluation of cell and gene therapies. Targeting of the subretinal fluid compartment (bleb) is critical to the procedure, especially if treatment of the cone-rich area centralis is required (i.e., visual streak [VS] in pigs). To our knowledge, this study is the first to investigate the influence of injection site placement on VS involvement in the pig eye.</p><p><strong>Methods: </strong>We performed 23-gauge pars plana vitrectomy followed by SR injection in 41 eyes of 21 animals (Sus scrofa domesticus). In 27 eyes (65.9%), the injection site was placed superior to the VS, and in 14 eyes (34.1%) it was placed inferior to it. Using intraoperative imaging, blebs were classified based on their propagation behavior relative to the VS.</p><p><strong>Results: </strong>In 79% of cases, blebs from inferior injection sites developed away from the VS, exhibiting a mean ± SEM vertical anisotropy (AP) of 0.67 ± 0.11. In contrast, blebs from superior injection sites tended to develop toward the VS with an AP of 1.27 ± 0.18 (P = 0.0070). Blebs developed away from the VS in only 41% of injections (P = 0.0212). Inferior blebs were orientated close to 0° (horizontal), whereas superior blebs displayed varied orientations with a mean angle of 56° (P = 0.0008).</p><p><strong>Conclusions: </strong>Bleb propagation was anisotropic (i.e., directionally biased) and dependent on injection site placement. Superior injection sites led to superior VS detachment. Morphological analysis suggested increased adhesion forces at the VS and superior vascular arcades. This study will aid the planning of surgeries for targeted subretinal delivery in pig models.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"41"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Initial Retinal Nerve Fiber Layer Loss and Risk of Diabetic Retinopathy Over a Four-Year Period. 最初视网膜神经纤维层缺损与四年内糖尿病视网膜病变的风险
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.5
Xiaoying Zhong, Huangdong Li, Shaoying Tan, Shaopeng Yang, Ziyu Zhu, Wenyong Huang, Weijing Cheng, Wei Wang
{"title":"Initial Retinal Nerve Fiber Layer Loss and Risk of Diabetic Retinopathy Over a Four-Year Period.","authors":"Xiaoying Zhong, Huangdong Li, Shaoying Tan, Shaopeng Yang, Ziyu Zhu, Wenyong Huang, Weijing Cheng, Wei Wang","doi":"10.1167/iovs.65.12.5","DOIUrl":"10.1167/iovs.65.12.5","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate whether the rapid rate of peripapillary retinal nerve fiber layer (pRNFL) thinning in short-term is associated with the future risk of developing diabetic retinopathy (DR).</p><p><strong>Methods: </strong>This prospective cohort study utilized 4-year follow-up data from the Guangzhou Diabetic Eye Study. The pRNFL thickness was measured by optical coherence tomography (OCT). DR was graded by seven-field fundus photography after dilation of the pupil. Correlations between pRNFL thinning rate and DR were analyzed using logistic regression. The additive predictive value of the prediction model was assessed using the C-index, net reclassification index (NRI), and integrated discriminant improvement index (IDI).</p><p><strong>Results: </strong>A total of 1012 patients with diabetes (1012 eyes) without DR at both baseline and 1-year follow-up were included in this study. Over the 4-year follow-up, 132 eyes (13%) developed DR. After adjusting for confounding factors, a faster rate of initial pRNFL thinning was significantly associated with the risk of DR (odds ratio per standard deviation [SD] decrease = 1.15, 95% confidence interval [CI] = 1.08 to 1.23, P < 0.001). Incorporating either the baseline pRNFL thickness or its thinning rate into conventional prediction models significantly improved the discriminatory power. Adding the rate of pRNFL thinning further enhanced the discriminative power compared with models with only baseline pRNFL thickness (C-index increased from 0.685 to 0.731, P = 0.040). The IDI and NRI were 0.114 and 0.463, respectively (P < 0.001).</p><p><strong>Conclusions: </strong>The rate of initial pRNFL thinning was associated with DR occurrence and improved discriminatory power of traditional predictive models. This provides new insights into the management and screening of DR.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"5"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glial Cell Responses and Gene Expression Dynamics in Retinas of Treated and Untreated RPE65 Mutant Dogs. 经治疗和未经治疗的 RPE65 突变体犬视网膜中神经胶质细胞的反应和基因表达动态。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.18
Tatyana Appelbaum, Evelyn Santana, David A Smith, William A Beltran, Gustavo D Aguirre
{"title":"Glial Cell Responses and Gene Expression Dynamics in Retinas of Treated and Untreated RPE65 Mutant Dogs.","authors":"Tatyana Appelbaum, Evelyn Santana, David A Smith, William A Beltran, Gustavo D Aguirre","doi":"10.1167/iovs.65.12.18","DOIUrl":"10.1167/iovs.65.12.18","url":null,"abstract":"<p><strong>Purpose: </strong>The long-term evaluation of RPE65 gene augmentation initiated in middle-aged RPE65 mutant dogs previously uncovered notable inter-animal and intra-retinal variations in treatment efficacy. The study aims to gain deeper insights into the status of mutant retinas and assess the treatment impact.</p><p><strong>Methods: </strong>Immunohistochemistry utilizing cell-specific markers and reverse transcription-quantitative PCR (RT-qPCR) analysis were conducted on archival retinal sections from normal and RPE65 mutant dogs.</p><p><strong>Results: </strong>Untreated middle-aged mutant retinas exhibited marked downregulation in the majority of 20 examined genes associated with key retinal pathways. These changes were accompanied by a moderate increase in microglia numbers, altered expression patterns of glial-neuronal transmitter recycling proteins, and gliotic responses in Müller glia. Analysis of advanced-aged mutant dogs revealed mild outer nuclear layer loss in the treated eye compared to moderate loss in the corresponding retinal regions of the untreated control eye. However, persistent Müller glial stress response along with photoreceptor synapse loss were evident in both treated and untreated eyes. Photoreceptor synaptic remodeling, infrequent in treated regions, was observed in all untreated advanced-aged retinas, accompanied by a progressive increase in microglial cells indicative of ongoing inflammation. Interestingly, about half of the examined genes showed similar expression levels between treated and untreated advanced-aged mutant retinas, with some reaching normal levels.</p><p><strong>Conclusions: </strong>Gene expression data suggest a shift from pro-degenerative mechanisms in middle-aged mutant retinas to more compensatory mechanisms in preserved retinal regions at advanced stages, despite ongoing degeneration. Such shift, potentially attributed to a number of surviving resilient cells, may influence disease patterns and treatment outcomes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"18"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TiO2-Nanoparticle-Enhanced Sonodynamic Therapy for Prevention of Posterior Capsular Opacification and Ferroptosis Exploration of Its Mechanism. TiO2-纳米粒子增强声动力疗法用于预防后囊翳和铁沉着症的机制探索
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.24
Yuanyuan Li, Pingjun Chang, Liming Xu, Zehui Zhu, Man Hu, Jiaying Cen, Siyan Li, Yun-E Zhao
{"title":"TiO2-Nanoparticle-Enhanced Sonodynamic Therapy for Prevention of Posterior Capsular Opacification and Ferroptosis Exploration of Its Mechanism.","authors":"Yuanyuan Li, Pingjun Chang, Liming Xu, Zehui Zhu, Man Hu, Jiaying Cen, Siyan Li, Yun-E Zhao","doi":"10.1167/iovs.65.12.24","DOIUrl":"10.1167/iovs.65.12.24","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the application and potential ferroptosis mechanisms of sonodynamic therapy (SDT) using titanium dioxide nanoparticles (TiO2-NPs) as sonosensitizers for the prevention of posterior capsule opacification (PCO).</p><p><strong>Methods: </strong>We fabricated TiO2-NP-coated intraocular lenses (TiO2-IOLs) using the spin-coating method, followed by ultrasound activation of the photosensitizer TiO2. In vitro experiments were performed with human lens epithelial cells (HLECs) to explore the appropriate concentration of TiO2 and ultrasonic parameters. Investigations included reactive oxygen species (ROS) generation, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) western blot analysis, lipid peroxidation assays, and transcriptomics analysis. Finally, TiO2-IOLs were implanted in rabbit eyes to explore the in vivo performance of SDT.</p><p><strong>Results: </strong>Through both in vitro and in vivo experiments, the study determined that the ultrasound parameters of 5-minute duration, 1-MHz frequency, 50% duty cycle, and 1.2-W/cm2 intensity were reliable and valid for killing HLECs without damaging other ocular structures. In vitro experiments demonstrated that SDT generated excess ROS, which disrupted the mitochondrial membrane potential and significantly reduced the GSH content. Additionally, the downregulation of GPX4, accumulation of lipid peroxides, and alteration of mitochondrial morphology were observed, suggesting that ferroptosis may be the underlying mechanism. The RNA-sequencing analysis results also showed an increase in the expression of multiple pro-ferroptosis genes and the ferroptosis marker gene PTGS2. Animal experiments preliminarily demonstrated the safety and effectiveness of SDT in treating PCO in vivo.</p><p><strong>Conclusions: </strong>TiO2-IOLs combined with SDT effectively prevented PCO by generating ROS and intracellular ferroptosis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"24"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multicenter Normative Data for Mesopic Microperimetry. 中焦显微透视测量的多中心规范数据。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.27
Maximilian Pfau, Jasleen K Jolly, Jason Charng, Leon von der Emde, Philipp L Müller, Georg Ansari, Kristina Pfau, Fred K Chen, Zhichao Wu
{"title":"Multicenter Normative Data for Mesopic Microperimetry.","authors":"Maximilian Pfau, Jasleen K Jolly, Jason Charng, Leon von der Emde, Philipp L Müller, Georg Ansari, Kristina Pfau, Fred K Chen, Zhichao Wu","doi":"10.1167/iovs.65.12.27","DOIUrl":"10.1167/iovs.65.12.27","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to provide a large, multi-center normative dataset for the Macular Integrity Assessment (MAIA) microperimeter and compare the goodness-of-fit and prediction interval calibration-error for a panel of hill-of-vision models.</p><p><strong>Methods: </strong>Microperimetry examinations of healthy eyes from five independent study groups and one previously available dataset were included (1137 tests from 531 eyes of 432 participants [223 women and 209 men]). Linear mixed models (LMMs) were fitted to the data to obtain interpretable hill-of-vision models. A panel of regression models to predict normative data was compared using cross-validation with site-wise splits. The mean absolute error (MAE) and miscalibration area (area between the calibration curve and the ideal diagonal) were evaluated as the performance measures.</p><p><strong>Results: </strong>Based on the parameters \"participant age,\" \"eccentricity from the fovea,\" \"overlap with the central fixation target,\" and \"eccentricity along the four principal meridians,\" a Bayesian mixed model had the lowest MAE (2.13 decibel [dB]; 95% confidence interval [CI] = 1.9-2.36 dB) and miscalibration area (0.13; 95% CI = 0.07-0.19). However, a parsimonious linear model provided a comparable MAE (2.17 dB; 95% CI = 1.93-2.4 dB) and a similar miscalibration area (0.14; 95% CI = 0.08-0.2).</p><p><strong>Conclusions: </strong>Normal variations in visual sensitivity on mesopic microperimetry can be effectively explained by a linear model that includes age and eccentricity. The dataset and a code vignette are provided for estimating normative values across a large range of retinal locations, applicable to customized testing patterns.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"27"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Factors Affecting Stimulus Duration Threshold for Depth Discrimination of Asynchronous Targets in the Intermediate Distance Range. 影响中距离范围内异步目标深度辨别的刺激持续时间阈值的因素。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.36
Yiya Chen, Zijiang J He, Teng Leng Ooi
{"title":"Factors Affecting Stimulus Duration Threshold for Depth Discrimination of Asynchronous Targets in the Intermediate Distance Range.","authors":"Yiya Chen, Zijiang J He, Teng Leng Ooi","doi":"10.1167/iovs.65.12.36","DOIUrl":"https://doi.org/10.1167/iovs.65.12.36","url":null,"abstract":"<p><strong>Purpose: </strong>Binocular depth discrimination in the near distance range (< 2 m) improves with stimulus duration. However, whether the same response-pattern holds in the intermediate distance range (approximately 2-25 m) remains unknown because the spatial coding mechanisms are thought to be different.</p><p><strong>Methods: </strong>We used the two-interval forced choice procedure to measure absolute depth discrimination of paired asynchronous targets (3, 6, or 16 arc min). The paired targets (0.2 degrees) were located over a distance and height range, respectively, of 4.5 to 7.0 m and 0.15 to 0.7 m. Experiment 1 estimated duration thresholds for binocular depth discrimination at varying target durations (40-1610 ms), in the presence of a 2 × 6 array of parallel texture-elements spanning 1.5 × 5.83 m on the floor. The texture-elements provided a visible background in the light-tight room (9 × 3 m). Experiment 2 used a similar setup to control for viewing conditions: binocular versus monocular and with versus without texture background. Experiment 3 compared binocular depth discrimination between brief (40, 80, and 125 ms) and continuous texture background presentation.</p><p><strong>Results: </strong>Stimulus duration threshold for depth discrimination decreased with increasing disparity in experiment 1. Experiment 2 revealed depth discrimination performance with texture background was near chance level with monocular viewing. Performance with binocular viewing degraded without texture background. Experiment 3 showed continuous texture background presentation enhances binocular depth discrimination.</p><p><strong>Conclusions: </strong>Absolute depth discrimination improves with target duration, binocular viewing, and texture background. Performance further improved with longer background duration underscoring the role of ground surface representation in spatial coding.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"36"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Predictors of Discordance Between Dry Eye Symptoms and Signs: Insights From the Sjögren's International Collaborative Clinical Alliance. 干眼症症状与体征不一致的预测因素:来自斯约格伦氏症国际临床合作联盟的启示。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.3
Fanxiu Xiong, Benjamin F Arnold, Thomas M Lietman, John A Gonzales
{"title":"Predictors of Discordance Between Dry Eye Symptoms and Signs: Insights From the Sjögren's International Collaborative Clinical Alliance.","authors":"Fanxiu Xiong, Benjamin F Arnold, Thomas M Lietman, John A Gonzales","doi":"10.1167/iovs.65.12.3","DOIUrl":"10.1167/iovs.65.12.3","url":null,"abstract":"<p><strong>Purpose: </strong>The diagnosis and management of dry eye disease (DED) could be complicated by the discordance between DED-related symptoms and signs. We performed a cross-sectional study to investigate the factors of and develop predictive models for the discrepancy in DED symptomatology.</p><p><strong>Methods: </strong>We used data from 3455 participants, 21 to 89 years old, from the Sjögren's International Collaborative Clinical Alliance study. We performed a multivariable stepwise linear regression model with backward elimination and Bayesian information criteria to select predictors for the discordance in DES symptomatology, which was defined as the difference between the rank score of Ocular Surface Disease Index 6 (OSDI-6) and the rank score of ocular staining score (OSS).</p><p><strong>Results: </strong>Ten predictors, such as \"vitality,\" \"immunomodulating drugs,\" sensory symptoms,\" and \"ethnicity,\" remained in the final models, achieving an adjusted R2 (aR2) of 0.35 (95% confidence interval [CI], 0.32-0.39). Specifically, medication use explained 19% (95% CI, 0.17-0.22) of the variance in the outcome, followed by medical history (aR2 = 0.18; 95% CI, 0.15-0.21). Health-related quality of life contributed 16% to the variance in the outcome (95% CI, 0.13-0.19), and, last, demographics contributed 11% (95% CI, 0.09-0.13).</p><p><strong>Conclusions: </strong>Our results suggest that individuals of Asian descent and those using immunomodulating medications often present with severe ocular signs that necessitate regular ophthalmological evaluations, even in the absence of proportionate ocular symptoms. Additionally, ocular symptoms, when accompanied by abnormal sensations in other parts of the body, could indicate systemic conditions that require further investigation and medical care.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"3"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive Pharmacokinetic Evaluation of High Melanin Binder Levofloxacin in Rabbits Shows Potential of Topical Eye Drops for Posterior Segment Treatment. 高黑色素粘合剂左氧氟沙星在兔子体内的全面药代动力学评估显示了局部滴眼液治疗后眼部疾病的潜力。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.14
Sina Bahrpeyma, Paulina Jakubiak, Rubén Alvarez-Sánchez, Antonello Caruso, Monika Leuthardt, Claudia Senn, Eva M Del Amo, Arto Urtti
{"title":"Comprehensive Pharmacokinetic Evaluation of High Melanin Binder Levofloxacin in Rabbits Shows Potential of Topical Eye Drops for Posterior Segment Treatment.","authors":"Sina Bahrpeyma, Paulina Jakubiak, Rubén Alvarez-Sánchez, Antonello Caruso, Monika Leuthardt, Claudia Senn, Eva M Del Amo, Arto Urtti","doi":"10.1167/iovs.65.12.14","DOIUrl":"10.1167/iovs.65.12.14","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this work was to understand the impact of melanin binding on ocular pharmacokinetics after administration of a high-binder model drug via different administration routes.</p><p><strong>Methods: </strong>We applied levofloxacin to pigmented and albino rabbits as eye drops (single and multiple), as well as by intravitreal and intravenous injections. Ocular tissues and plasma were analyzed for levofloxacin concentrations with liquid chromatography-mass spectrometry (LC-MS/MS), and pharmacokinetic parameters were calculated.</p><p><strong>Results: </strong>The data show enrichment of levofloxacin and weeks-long retention in pigmented tissues. Upon intravitreal injection, the area under the curve (AUC) values in pigmented tissues were about 9 to 15 times higher than the respective values in the albino rabbits, but this difference expanded to 255- to 951-fold following topical eye drop administration. Multiple dosing of eye drops led to substantial accumulation of levofloxacin in the pigmented tissues: AUC values were 3 to 12 times higher than after intravitreal injection. The AUCs were much lower after single topical or intravenous drug administrations. High drug levels (0.1-35 µM) were always observed in the neural retinas of pigmented eyes; the highest exposure was seen after intravitreal administration followed by multiple doses of topical drops. Single topical instillation and intravenous injections to the albino rabbits resulted in vitreal bioavailability values of 0.009% and 0.003%, respectively.</p><p><strong>Conclusions: </strong>Melanin binding can be used to achieve targeted drug delivery and extended retention in pigmented ocular tissues. The results from topical multiple dosing experiments suggest that eye drop treatment may yield drug exposures and responses comparable to intravitreal delivery, even in the retinal pigment epithelium and choroid.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"14"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A New Retest-Stable Tortuosity Metric for Retinal Vessel Analyses. 用于视网膜血管分析的全新重测稳定扭曲度指标
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.30
Samuel David Giesser, Ferhat Turgut, Amr Saad, Chiara Sommer, Yukun Zhou, Siegfried Karl Wagner, Pearse Andrew Keane, Matthias Becker, Delia Cabrera DeBuc, Gábor Márk Somfai
{"title":"A New Retest-Stable Tortuosity Metric for Retinal Vessel Analyses.","authors":"Samuel David Giesser, Ferhat Turgut, Amr Saad, Chiara Sommer, Yukun Zhou, Siegfried Karl Wagner, Pearse Andrew Keane, Matthias Becker, Delia Cabrera DeBuc, Gábor Márk Somfai","doi":"10.1167/iovs.65.12.30","DOIUrl":"10.1167/iovs.65.12.30","url":null,"abstract":"<p><strong>Purpose: </strong>Existing retinal vessel tortuosity metrics lack standardization and retest reliability, hindering their clinical utility. Our study addresses this gap by introducing a novel metric, coined as the \"vascular curvature index\" (VCI), to enhance accuracy and consistency in biomarkers associated with medical conditions. We assess VCI's performance in terms of retest reliability in healthy subjects to transform early detection and monitoring approaches for various diseases.</p><p><strong>Methods: </strong>We recruited 44 patients for a single-session study, capturing fundus images before and after a five-minute break. Using AutoMorph, we generated vessel segmentation maps and evaluated retest reliability using multiple tortuosity metrics. The VCI was introduced and statistically compared to existing metrics. We performed a paired one-sided t-test to test for significantly improved retest reliability of our newly proposed metric. We analyzed distribution histograms, Fisher-Pearson coefficient of skewness, and correlation matrices for further insights.</p><p><strong>Results: </strong>VCI is the most retest-reliable metric, statistically surpassing other curvature metrics, except inverse spherical radius tortuosity. With a somewhat negatively distributed pattern (coefficient of skewness of -0.52), VCI exhibits the strongest correlation with the second most retest-reliable metric; inverse-radius-tortuosity (Pearson and Spearman correlation of 0.7 and 0.72, respectively). Its correlation with angle-tortuosity is lower (Pearson and Spearman correlation of 0.05 and 0.07, respectively).</p><p><strong>Conclusions: </strong>The VCI emerges as a highly retest-reliable metric with a relatively normal distribution in healthy patients. Further investigation is warranted to evaluate its clinical performance in real-world applications, potentially influencing proactive healthcare interventions and personalized treatment decision-making.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"30"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Semi-Automated Analysis of Dome-Shaped Macula in Preterm and Full-Term Infants Using Handheld Swept-Source Optical Coherence Tomography. 使用手持式扫源光学相干断层扫描半自动分析早产儿和足月儿的穹顶形黄斑
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.35
Joshua N Dang, Jolan Wu, Yujiao Zheng, Jason J Bunk, Emily K Tam, Karen E Lee, Sumner E Lawson, Tatiana R Monger, Alex T Legocki, John P Kelly, Obiageri Egeolu, Leona Ding, Ruikang K Wang, Kristina Tarczy-Hornoch, Michelle T Cabrera
{"title":"Semi-Automated Analysis of Dome-Shaped Macula in Preterm and Full-Term Infants Using Handheld Swept-Source Optical Coherence Tomography.","authors":"Joshua N Dang, Jolan Wu, Yujiao Zheng, Jason J Bunk, Emily K Tam, Karen E Lee, Sumner E Lawson, Tatiana R Monger, Alex T Legocki, John P Kelly, Obiageri Egeolu, Leona Ding, Ruikang K Wang, Kristina Tarczy-Hornoch, Michelle T Cabrera","doi":"10.1167/iovs.65.12.35","DOIUrl":"10.1167/iovs.65.12.35","url":null,"abstract":"<p><strong>Purpose: </strong>Dome-shaped macula (DSM) is known to occur in highly myopic adults and, recently, preterm infants. This study uses investigational handheld swept-source optical coherence tomography (SS-OCT) to further characterize infantile DSM.</p><p><strong>Methods: </strong>In this prospective, observational study, preterm infants undergoing retinopathy of prematurity screening and full-term infants within 72 hours of birth were imaged. Two trained graders assessed macular features, including DSM, subretinal fluid, and macular edema. A semi-automated program measured foveal immaturity, dome height, and diameter.</p><p><strong>Results: </strong>Two hundred seventeen imaging sessions from 50 full-term and 30 preterm infants were included (46% female, preterm birth weight 1038 ± 335 g, and gestational age 28.7 ± 3.1 weeks). DSM occurred in 40% preterm versus 14% full-term infants (P = 0.01). Mean postmenstrual age at first DSM diagnosis was 38.4 ± 0.0 weeks among preterm and 40.4 ± 1.1 weeks among full-term infants (P < 0.001). Dome height and diameter measured 55.67 ± 44.22 µm and 3583.15 ± 1090.35 µm for preterm versus 88.37 ± 44.73 µm and 3581.97 ± 355.07 µm for full-term infants (P = 0.24 and P = 0.96, respectively). All 27 images (11 preterm and 7 full-term infants) with 3-dimensional analysis had round dome configuration. No other associations were seen, including macular fluid (P = 0.17).</p><p><strong>Conclusions: </strong>Infants frequently exhibit DSM without an association with macular fluid. Preterm infants were more likely than full-term infants to have DSM. Unlike DSM in children and adults, infantile DSM configuration is mostly round rather than ridge-shaped.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"35"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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