Translational Vision Science & Technology最新文献

{"title":"Quantification of the Anterior-Centripetal Movement of the Ciliary Muscle During Accommodation Using Dynamic OCT Imaging.","authors":"Iulen Cabeza-Gil, Marco Ruggeri, Fabrice Manns","doi":"10.1167/tvst.14.1.17","DOIUrl":"10.1167/tvst.14.1.17","url":null,"abstract":"<p><strong>Purpose: </strong>Although the lens undoubtedly plays a major role in presbyopia, altered lens function could be in part secondary to age-related changes of the ciliary muscle. Ciliary muscle changes with accommodation have been quantified using optical coherence tomography, but so far these studies have been limited to quantifying changes in ciliary muscle thickness, mostly at static accommodative states. Quantifying ciliary muscle thickness changes does not effectively capture the dynamic anterior-centripetal movement of the ciliary muscle during accommodation. To address this issue, we present a method to quantify the movement of the ciliary muscle during accommodation using trans-scleral optical coherence tomography images obtained dynamically.</p><p><strong>Methods: </strong>An image processing framework including distortion correction, geometric transformation, and Procrustes analysis, was used to quantify the anterior-centripetal movement of the ciliary muscle apex and centroid during accommodation. The method was applied in a preliminary study to quantify ciliary muscle displacement and its relation to lens thickness change with accommodation on two young adults and two prepresbyopes.</p><p><strong>Results: </strong>The magnitude and the direction relative to the pupil plane of the apex/centroid displacement in response to a two diopters (2D) stimulus were 0.16/0.20 mm at 11.3°/30.5° and 0.26/0.34 mm at 6.6°/33.2° for the young adults and 0.20/0.20 mm at 29.7°/40.6° and 0.24/0.40 mm at 33.0°/31.7° for the prepresbyopes, respectively.</p><p><strong>Conclusions: </strong>This study demonstrates the feasibility of quantifying dynamic anterior-centripetal movement of the ciliary muscle during accommodation using optical coherence tomography. The method better captures the functional response of the muscle than the quantification of thickness changes.</p><p><strong>Translational relevance: </strong>We provide a method that holds potential to better understand the age-related changes of the ciliary muscle on presbyopia.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 1","pages":"17"},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characteristics and In Vivo Confocal Microscopic Study in Candida Keratitis.","authors":"Yan Peng, Qiankun Chen, Yuan Wei, Leying Wang, Zijun Zhang, Zhenyu Wei, Jinding Pang, Bo Peng, Qingquan Shi, Zhiqun Wang, Yang Zhang, Kexin Chen, Xizhan Xu, Qingfeng Liang","doi":"10.1167/tvst.14.1.23","DOIUrl":"10.1167/tvst.14.1.23","url":null,"abstract":"<p><strong>Purpose: </strong>To clarify the clinical and imaging characteristics of Candida keratitis using in vivo confocal microscopy (IVCM) for improved early diagnosis and management.</p><p><strong>Methods: </strong>A retrospective study of 40 patients with Candida keratitis at Beijing Tongren Hospital from January 2015 to December 2023 was conducted. Data included demographics, risk factors, clinical assessments, lab tests, and IVCM images. Ex vivo confocal microscopy and methylene blue staining of Candida colonies were also analyzed to complement the findings.</p><p><strong>Results: </strong>Key risk factors identified were topical steroid use, intraocular surgery history, and systemic diseases. Common clinical signs included multifocal infiltration, cream-colored infiltration, and blurred boundary lesions. IVCM on 37 eyes (92.5%) consistently showed round, highly reflective Candida spores, and short rod-shaped spores in some cases. Spores exhibited two patterns: caviar-like clusters (51.4%) and sand-like dispersion (89.2%). Multifocal infiltration was significantly associated with a greater prevalence of clustered spores (75.0% vs. 33.3%; P < 0.05). Candida pseudo-hyphae appeared as beaded (91.7%) or lotus root-shaped (41.7%), highly reflective structures. These IVCM findings closely matched colony ex vivo confocal microscopy and light microscopy observations. After treatment, 45% of patients required surgery owing to minimal improvement in best-corrected visual acuity. Poor outcomes were linked to cream-colored infiltration, blurred lesions boundaries, hypopyon, high inflammatory cell density, and deep Candida infiltration (P < 0.05). Clustered spores suggested better outcomes, but lacked statistical significance (P > 0.05).</p><p><strong>Conclusions: </strong>IVCM effectively identifies characteristic spores and pseudo-hyphae in Candida keratitis, facilitating early detection and timely management, particularly in cases with multifocal infiltration and blurred boundary lesions.</p><p><strong>Translational relevance: </strong>IVCM works well for the early diagnosis of Candida keratitis, especially in cases of deep corneal stromal infiltration or corneal interface infection after corneal transplantation.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 1","pages":"23"},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Associations Between Myopia and Fundus Tessellation in School Children: A Comparative Analysis of Macular and Peripapillary Regions Using Deep Learning.","authors":"Dan Huang, Xiao Lin, Hui Zhu, Saiguang Ling, Zhou Dong, Xin Ke, Tengfei Long, Yingxiao Qian, Qi Yan, Rui Li, Hua Zhong, Hu Liu","doi":"10.1167/tvst.14.1.4","DOIUrl":"10.1167/tvst.14.1.4","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the refractive differences among school-aged children with macular or peripapillary fundus tessellation (FT) distribution patterns, using fundus tessellation density (FTD) quantified by deep learning (DL) technology.</p><p><strong>Methods: </strong>The cross-sectional study included 1942 school children aged six to 15 years, undergoing ocular biometric parameters, cycloplegic refraction, and fundus photography. FTD was quantified for both the macular (6 mm) and peripapillary (4 mm) regions, using DL-based image processing applied to 45° color fundus photographs. Eyes exhibiting tessellation were classified into two groups: the macular distribution group had greater FTD in the macular area, while the peripapillary distribution group had higher FTD in the peripapillary area, allowing for a comparative analysis of axial length (AL), corneal radius, and refraction.</p><p><strong>Results: </strong>Participants had a median age of 13 years and a median spherical equivalent (SE) of -0.75 D. The macular distribution group exhibited significantly larger AL (24.13 mm vs. 23.93 mm, P < 0.001) and more myopic refraction (-1.13 D vs. -0.75 D, P < 0.001) compared to the peripapillary group. A higher prevalence of macular-distributed FT was noted in the myopic groups (χ2 = 131.675, P < 0.001). SE negatively correlated with macular (r = -0.238) and peripapillary FTD (r = -0.195), while AL positively correlated with FTD in both regions (r = 0.308; r = 0.265) (all P < 0.001).</p><p><strong>Conclusions: </strong>The macular FT distribution pattern is significantly associated with larger AL and greater myopic refraction in school-aged children, suggesting its potential as a marker for identifying children at risk of progressing myopia.</p><p><strong>Translational relevance: </strong>DL analysis precisely identifies FT distribution patterns, potentially enhancing early detection of high-risk myopia in populations.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 1","pages":"4"},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance on Activities of Daily Living and User Experience When Using Artificial Intelligence by Individuals With Vision Impairment.","authors":"William Seiple, Hilde P A van der Aa, Fernanda Garcia-Piña, Izekiel Greco, Calvin Roberts, Ruth van Nispen","doi":"10.1167/tvst.14.1.3","DOIUrl":"10.1167/tvst.14.1.3","url":null,"abstract":"<p><strong>Purpose: </strong>This study assessed objective performance, usability, and acceptance of artificial intelligence (AI) by people with vision impairment. The goal was to provide evidence-based data to enhance technology selection for people with vision loss (PVL) based on their loss and needs.</p><p><strong>Methods: </strong>Using a cross-sectional, counterbalanced, cross-over study involving 25 PVL, we compared performance using two smart glasses (OrCam and Envision Glasses) and two AI apps (Seeing AI and Google Lookout). We refer to these as assistive artificial intelligence implementations (AAIIs). Completion and timing were quantified for three task categories: text, text in columns, and searching and identifying. Usability was evaluated with the System Usability Scale (SUS).</p><p><strong>Results: </strong>The odds ratios (ORs) of being able to complete Text tasks were significantly higher when using AAIIs compared to the baseline. OR when performing \"Searching and Identifying\" tasks varied among AAIIs, with Seeing AI and Envision improving the performance of more tasks than Lookout or OrCam. Participants expressed high satisfaction with the AAIIs.</p><p><strong>Conclusions: </strong>Despite the findings that performance on some tasks and when using some AAIIs did not result in a greater number of PVL being able to complete the tasks, there was overall high satisfaction, reflecting an acceptance of AI as an assistive technology and the promise of this developing technology.</p><p><strong>Translational relevance: </strong>This evidence-based performance data provide guidelines for clinicians when recommending an AAII to PVL.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 1","pages":"3"},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perfusion Capacity as a Predictive Index for Assessing Visual Functional Recovery in Patients With Idiopathic Epiretinal Membrane.","authors":"Jinlian Zhan, Chen Chen, Tong Wang, Qi Zhang, Xia Huang, Lin Lu, Xiujuan Zhao","doi":"10.1167/tvst.14.1.19","DOIUrl":"10.1167/tvst.14.1.19","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates the association between visual function and retinal vasculature metrics, particularly perfusion capacity (PC), in eyes with idiopathic epiretinal membrane (iERM), using optical coherence tomography angiography (OCTA).</p><p><strong>Methods: </strong>This retrospective study includes 30 eyes from 30 iERM patients who had surgery, with a three-month follow-up period. In addition, 28 eyes from 28 healthy individuals served as a control group. We measured best-corrected visual acuity (BCVA), retinal sensitivity, vascular density (VD), perfusion area (PA), PC, and retinal thickness (RT). OCTA scans assessed both the superficial vascular complex (SVC) and deep vascular complex (DVC) in 3 × 3 mm2 and 6 × 6 mm2 regions. Associations between retinal vasculature metrics and visual outcomes were analyzed.</p><p><strong>Results: </strong>Postoperatively, significant improvements were observed in both BCVA and retinal sensitivity (both P < 0.001). In the SVC layer, VD and PA were significantly decreased (both P < 0.001), whereas PC in the SVC increased significantly (P < 0.001). Higher preoperative PC in the SVC was associated with greater postoperative improvements in retinal sensitivity. Postoperative retinal sensitivity was negatively associated with age (β = -0.53, P = 0.001) and retinal thickness in 3 × 3 mm2 region (β = -0.39, P = 0.013) but positively associated with preoperative retinal sensitivity (β = 1.10, P < 0.001) and PC in the SVC within 3 × 3 mm2 region (β = 0.49, P = 0.023).</p><p><strong>Conclusions: </strong>PC offers a novel approach to evaluating retinal microcirculation and visual prognosis in iERM. Preoperative PC in the SVC serves as a reliable predictive index for predicting postoperative visual recovery.</p><p><strong>Translational relevance: </strong>The PC, as a novel indicator of retinal blood flow, not only reflects the condition of the blood vessels but is also associated with retinal sensitivity.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 1","pages":"19"},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Resolution OCT Reveals Age-Associated Variation in the Region Posterior to the External Limiting Membrane.","authors":"Muhammad Usman Jamil, Jungeun Won, Stefan B Ploner, Anna Marmalidou, Hiroyuki Takahashi, Stephanie Kaiser, Yunchan Hwang, Omar Abu-Qamar, Antonio Yaghy, Andre J Witkin, Peter Y Zhao, Shilpa Desai, Jay S Duker, Andreas Maier, James G Fujimoto, Nadia K Waheed","doi":"10.1167/tvst.14.1.16","DOIUrl":"10.1167/tvst.14.1.16","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate visibility of a sub-band posterior to the external limiting membrane (ELM) and assess its age-associated variation.</p><p><strong>Methods: </strong>In a retrospective cross-sectional study, normal eyes were imaged using a high-resolution spectral-domain optical coherence tomography (SD-OCT) prototype (2.7-µm axial resolution). Volume fusion of six sequential scans (each 500 × 500 A-scans over 6 mm × 6 mm) was performed in the motion correction and volume reconstruction in OCT (MoReOCT) framework to enhance feature visibility in OCT. The subjects were divided into three groups: young (21-40 years old), middle (41-60 years old), and older (>60 years old). Three expert graders assessed the visibility of the sub-band on B-scans, and its A-scan intensity relative to ELM intensity (peak intensity ratio) was measured.</p><p><strong>Results: </strong>Forty-four eyes of 44 subjects were imaged. The sub-band, tentatively attributed to the photoreceptor myoid, can be visualized under high-resolution OCT. The B-scan gradings showed that sub-band visibility increased with age (visible in 16.7%, 47.2%, and 66.7% of the young, middle, and older age groups, respectively). The gradings were statistically different among age groups at 1 mm and 2 mm nasal and 1 mm and 2 mm temporal (P < 0.04) from the foveal center. Similarly, the mean peak intensity ratios of the sub-band to the ELM were 71.6%, 77.5%, and 85.2% in the young, middle, and older age groups, respectively, and were positively correlated with age at 1 mm temporal (P = 0.012) and 2 mm temporal (P < 0.001).</p><p><strong>Conclusions: </strong>High-resolution OCT, combined with advanced volume fusion, enables visualization of the photoreceptor myoid and investigation of its age-associated variations.</p><p><strong>Translational relevance: </strong>Investigating the sub-band can advance our understanding of photoreceptors and their association with aging and disease pathogenesis.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 1","pages":"16"},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of a Novel Ultra-Widefield Three-Color Scanning Laser Ophthalmoscope to Other Retinal Imaging Modalities in Chorioretinal Lesion Imaging.","authors":"Ines D Nagel, Anna Heinke, Akshay P Agnihotri, Shaden Yassin, Lingyun Cheng, Andrew S Camp, Nathan L Scott, Fritz Gerald P Kalaw, Shyamanga Borooah, Dirk-Uwe G Bartsch, Arthur J Mueller, Nehal Mehta, William R Freeman","doi":"10.1167/tvst.14.1.11","DOIUrl":"10.1167/tvst.14.1.11","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the assessment of clinically relevant retinal and choroidal lesions as well as optic nerve pathologies using a novel three-wavelength ultra-widefield (UWF) scanning laser ophthalmoscope with established retinal imaging techniques for ophthalmoscopic imaging.</p><p><strong>Methods: </strong>Eighty eyes with a variety of retinal and choroidal lesions were assessed on the same time point using Topcon color fundus photography (CFP) montage, Optos red/green (RG), Heidelberg SPECTRALIS MultiColor 55-color montage (MCI), and novel Optos red/green/blue (RGB). Paired images of the optic nerve, retinal, or choroidal lesions were initially diagnosed based on CFP imaging. The accuracy of the imaging was then evaluated in comparison to CFP using a grading scale ranging from -1 (losing imaging information) to +1 (gaining imaging information).</p><p><strong>Results: </strong>Eighty eyes of 43 patients with 116 retinal or choroidal pathologies, as well as 59 eyes with optic nerve imaging using CFP, MCI, RG, and RGB, were included in this study. Across all subgroups, RGB provided significantly more accurate clinical imaging with CFP as ground truth and compared to other modalities. This was true comparing RGB to both RG (P = 0.0225) and MCI (P < 0.001) overall. Although RGB provided more accurate clinical information overall, it was inferior to RG for melanocytic choroidal lesions (P = 0.011).</p><p><strong>Conclusions: </strong>RGB can be considered as a useful tool to detect characteristics of central, midperipheral, and peripheral retinal lesions. Regarding melanocytic choroidal lesions, RGB was inferior to RG, and MCI was inferior to both RG and RGB modalities due to color changes.</p><p><strong>Translational relevance: </strong>Traditional retinal ultra-widefield imaging uses two wavelengths. Here, we evaluated three wavelengths for ultra-widefield imaging. We examined new optics (basic science) effect on patient imaging (clinical care).</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 1","pages":"11"},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Rabbit Model of Meibomian Gland Dysfunction-Induced Dry Eye.","authors":"Annabelle Gallois-Bernos, Lichun Zhong, Mingqi Bai, Caroline A Blackie","doi":"10.1167/tvst.14.1.28","DOIUrl":"10.1167/tvst.14.1.28","url":null,"abstract":"<p><strong>Purpose: </strong>The objective of this three-phase study was to develop a model of mild to moderate evaporative dry eye to be used to evaluate tear film stability endpoints during product development.</p><p><strong>Methods: </strong>Rabbits were sedated prior to ophthalmic cautery of meibomian gland orifices. The orifices of eyelid meibomian glands were half-cauterized (to yield obstruction of every other meibomian gland orifices), fully cauterized (to yield obstruction of all meibomian gland orifices), or untreated. The primary outcome measures were model repeatability, tear film break-up time (TBUT), non-invasive tear break-up time (NIBUT), and model confirmation with daily artificial tears. Other examinations included Draize score, tear production, fluorescein staining, eschar, and histopathology.</p><p><strong>Results: </strong>Cauterization was well tolerated in all phases. In phase I, TBUT was significantly decreased compared to baseline on days 14, 21, 28, and 35 in fully cauterized meibomian gland orifices but not in half-cauterized meibomian gland orifices. In phase II, both NIBUT and TBUT were similarly and significantly reduced in the fully cauterized meibomian gland orifices compared to the control eyes on days 7, 9, 14, and 28. In the confirmation phase, the administration of eye drops significantly improved NIBUT over the course of the study.</p><p><strong>Conclusions: </strong>A rabbit model of dry eye was successfully and safely created through the obstruction of meibomian gland orifices by cautery, which yielded a significant reduction in tear film stability. A quantifiable benefit of artificial tears relative to untreated control was demonstrated within the model.</p><p><strong>Translational relevance: </strong>When the model is deployed, the utility and efficacy of therapeutic formulations can be evaluated.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 1","pages":"28"},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corneal Stromal Stem Cell-Derived Extracellular Vesicles Attenuate ANGPTL7 Expression in the Human Trabecular Meshwork.","authors":"Faycal Moujane, Chi Zhang, Robert Knight, John Y Lee, Sophie X Deng, Jie J Zheng","doi":"10.1167/tvst.14.1.21","DOIUrl":"10.1167/tvst.14.1.21","url":null,"abstract":"<p><strong>Purpose: </strong>Regulating intraocular pressure (IOP), mainly via the trabecular meshwork (TM), is critical in developing glaucoma. Whereas current treatments aim to lower IOP, directly targeting the dysfunctional TM tissue for therapeutic intervention has proven challenging. In our study, we utilized Dexamethasone (Dex)-treated TM cells as a model to investigate how extracellular vesicles (EVs) from immortalized corneal stromal stem cells (imCSSCs) could influence ANGPTL7 and MYOC genes expression within TM cells.</p><p><strong>Methods: </strong>Human TM cell lines were isolated and cultured from donor corneoscleral rims. EVs were purified from imCSSC conditioned media (CM) using size exclusion chromatography and characterized by nanoparticle tracking analysis, transmission electron microscopy (TEM), and ExoView technology. TM cells were treated with either Dex alone or with EVs for 5 days. Quantitative polymerase chain reaction (PCR) was carried out to quantify the mRNA level of MYOC and ANGPTL7.</p><p><strong>Results: </strong>A notable increase in the expression levels of MYOC and ANGPTL7 genes was observed compared with untreated TM cells (control). Furthermore, upon comparing Dex-treated TM cells with those receiving both Dex and EV treatments, a statistically significant reduction in ANGPTL7 expression (P < 0.05) was detected.</p><p><strong>Conclusions: </strong>The present study demonstrates that imCSSCs-derived EVs can effectively decrease the expression of ANGPLT7, a gene associated with fibrosis and implicated in the abnormal elevation of IOP in patients with glaucoma.</p><p><strong>Translational relevance: </strong>Our study shows that imCSSC-derived EVs can specifically target ANGPTL7 expression, making them a promising preclinical therapy for glaucoma.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 1","pages":"21"},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ocular Safety and Toxicology of Subretinal Gene Therapy With rAAV.hPDE6A in Nonhuman Primates.","authors":"Immanuel P Seitz, Fabian Wozar, Guy Alex Ochakovski, Felix F Reichel, Sven Korte, Birgit Korbmacher, Barbara Wilhelm, Daniela Süsskind, Karl-Ulrich Bartz-Schmidt, M Dominik Fischer, Tobias Peters","doi":"10.1167/tvst.14.1.29","DOIUrl":"10.1167/tvst.14.1.29","url":null,"abstract":"<p><strong>Purpose: </strong>Reports of gene therapy-associated retinal atrophies and inflammation have highlighted the importance of preclinical safety assessments of adeno-associated virus (AAV) vector systems. We evaluated in nonhuman primates (NHPs) the ocular safety and toxicology of a novel AAV gene therapy targeting retinitis pigmentosa caused by mutations in PDE6A, which has since been used in a phase I/II clinical trial (NCT04611503).</p><p><strong>Methods: </strong>A total of 34 healthy cynomolgus animals (Macaca fascicularis) were treated with subretinal injections of rAAV.hPDE6A and followed over 13 weeks. Three dose levels (low: 1 × 1011, intermediate: 5 × 1011, and high: 1 × 1012 vector genomes [vg]) were compared to sham-injected controls. Safety and toxicity were determined using ophthalmic examinations, electroretinography, ocular histology, and retinal imaging.</p><p><strong>Results: </strong>At the low and intermediate doses, inflammation was mild, electroretinography response was unimpeded, and histology results were in line with surgically induced changes. In contrast, three high-dose animals displayed atrophic changes of the retina and abnormalities in electroretinography, which were considered test article related and adverse.</p><p><strong>Conclusions: </strong>A single subretinal injection of up to 5 × 1011 vg was well tolerated, and a 10-fold lower dose of 5 × 1010 vg was chosen as the starting dose for the ongoing phase I/II clinical trial. Atrophic retinal changes and abnormalities in electroretinography emerged as dose-limiting findings in the high-dose cohort.</p><p><strong>Translational relevance: </strong>This study demonstrates that treatment candidate rAAV.PDE6A was well tolerated in NHPs. Occurrence of retinal atrophy as a dose-limiting finding highlights the importance of further study into the mechanisms of atrophy induction after retinal gene therapy.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 1","pages":"29"},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}