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Genotype-phenotype Correlations of Ocular Posterior Segment Abnormalities in Marfan Syndrome 马凡氏综合征眼后节异常的基因型与表型相关性
Ophthalmology science Pub Date : 2024-04-06 DOI: 10.1016/j.xops.2024.100526
Yan Liu BM , Yuqiao Ju MM , Tian-hui Chen MM , Yong-xiang Jiang MD, PhD
{"title":"Genotype-phenotype Correlations of Ocular Posterior Segment Abnormalities in Marfan Syndrome","authors":"Yan Liu BM ,&nbsp;Yuqiao Ju MM ,&nbsp;Tian-hui Chen MM ,&nbsp;Yong-xiang Jiang MD, PhD","doi":"10.1016/j.xops.2024.100526","DOIUrl":"10.1016/j.xops.2024.100526","url":null,"abstract":"<div><h3>Purpose</h3><p>Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the <em>f</em><em>ibrillin-1</em> ( (<em>FBN1</em>). In addition to typical phenotypes such as ectopia lentis (EL) and aortic dilation, patients with MFS are prone to ocular posterior segment abnormalities, including retinal detachment (RD), maculopathy, and posterior staphyloma (PS). This study aims to investigate the correlations between <em>FBN1</em> genotype and posterior segment abnormalities within a Chinese cohort of MFS.</p></div><div><h3>Design</h3><p>Retrospective study.</p></div><div><h3>Participants</h3><p>One hundred twenty-one eyes of 121 patients with confirmed <em>FBN1</em> mutations between January 2015 and May 2023 were included.</p></div><div><h3>Methods</h3><p>Comprehensive ophthalmic examination findings were reviewed, and the incidence of RD, atrophic, tractional, and neovascular maculopathy (ATN classification system), and PS was analyzed between different genotype groups. Only the more severely affected eye from each patient was included.</p></div><div><h3>Main Outcome Measures</h3><p>Clinical features and risk factors.</p></div><div><h3>Results</h3><p>Of 121 patients, 60 eyes (49.59%) exhibited posterior segment abnormalities, including RD (4, 3.31%), maculopathy (47, 38.84%), and PS (54, 44.63%). The mean age was 11.53 ± 11.66 years, with 79.34% of patients &lt;20 years old. The location and region of mutations were found to be associated with the incidence of maculopathy (<em>P</em> = 0.013, <em>P</em> = 0.033) and PS (<em>P</em> = 0.043, <em>P</em> = 0.036). Mutations in the middle region had a lower incidence of maculopathy and PS (<em>P</em> = 0.028 and <em>P</em> = 0.006, respectively) than those in C-terminal region. Mutations in the transforming growth factor-β (TGF-β) regulating sequence exhibited a higher incidence of maculopathy and PS (<em>P</em> = 0.020, <em>P</em> = 0.040). Importantly, the location and region of mutations were also associated with the incidence of atrophic maculopathy (<em>P</em> = 0.013 and <em>P</em> = 0.033, respectively). Mutations in the middle region had a significantly lower probability of atrophic maculopathy (<em>P</em> = 0.006), while mutations in the TGF-β regulating region had a higher incidence of atrophic maculopathy (<em>P</em> = 0.020).</p></div><div><h3>Conclusions</h3><p>Maculopathy and PS were associated with the location and region of <em>FBN1</em> mutations. Patients with mutations in the TGF-β regulating region faced an increased risk of developing retinopathy.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000629/pdfft?md5=23f4c4d6dcf46bbd8a9c20cbbc318ed9&pid=1-s2.0-S2666914524000629-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of Methods of Clinical Trial Emulation Utilizing Data From the Comparison of AMD Treatment Trial (CATT) and the IRIS® Registry 利用老年性黄斑病变治疗对比试验 (CATT) 和 IRIS® 注册表数据进行临床试验仿真的方法比较
Ophthalmology science Pub Date : 2024-04-03 DOI: 10.1016/j.xops.2024.100524
Helene Fevrier MPH , Andrew LaPrise BS , Michael Mbagwu MD , Theodore Leng MD, MS , Aracelis Z. Torres PhD, MPH , Durga S. Borkar MD, MMCi
{"title":"Comparison of Methods of Clinical Trial Emulation Utilizing Data From the Comparison of AMD Treatment Trial (CATT) and the IRIS® Registry","authors":"Helene Fevrier MPH ,&nbsp;Andrew LaPrise BS ,&nbsp;Michael Mbagwu MD ,&nbsp;Theodore Leng MD, MS ,&nbsp;Aracelis Z. Torres PhD, MPH ,&nbsp;Durga S. Borkar MD, MMCi","doi":"10.1016/j.xops.2024.100524","DOIUrl":"10.1016/j.xops.2024.100524","url":null,"abstract":"<div><h3>Purpose</h3><p>We used exact matching and inverse propensity score weighting (IPSW) using real-world data (RWD) from the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) to emulate the 2 pro re nata (<em>prn</em>) treatment arms from the Comparison of AMD Treatment Trial (CATT) and to compare the outcomes of the RWD arms to the 2 monthly treatment arms from the clinical trial.</p></div><div><h3>Design</h3><p>Retrospective cohort study utilizing deidentified electronic health record registry data and patient-level deidentified clinical trial data.</p></div><div><h3>Subjects</h3><p>All treatment-naive patient eyes with neovascular age-related macular degeneration treated with ranibizumab or bevacizumab only for 1 year from either the CATT or the IRIS Registry.</p></div><div><h3>Methods</h3><p>Patients were identified in the IRIS Registry between October 1, 2015 and December 31, 2019. After all nonimaging-based inclusion and exclusion criteria from the CATT were applied, patient eyes receiving bevacizumab or ranibizumab only on a <em>prn</em> basis were identified as the eligible cohort. Exact matching and ISPW was applied based on age, gender, and baseline visual acuity.</p></div><div><h3>Main Outcome Measures</h3><p>Mean change in visual acuity, in approximated ETDRS letters, between baseline and 1 year for the IRIS Registry prn treatment arms generated by exact matching and IPSW.</p></div><div><h3>Results</h3><p>We identified 427 eyes treated with ranibizumab <em>prn</em> and 771 eyes treated with bevacizumab <em>prn</em>. Using exact matching, 98% (n = 281) of CATT patient eyes in the bevacizumab monthly treatment arm and 87% (n = 261) of CATT patient eyes in the ranibizumab monthly treatment arm were matched to a patient eye in the IRIS Registry. For the ranibizumab <em>prn</em> treatment arm, patient eyes generated using exact matching gained 1.9 letters and those generated using IPSW gained 2.8 letters (exact matching: 1.9 letters ± 14.0 vs. IPSW: 2.8 letters ± 15.0 letters, <em>P</em> = 0.43). For the bevacizumab <em>prn</em> treatment arm, patient eyes generated using exact matching gained 2.4 letters and those generated using IPSW gained 2.1 letters (exact matching: 2.4 letters ± 15.4 vs. IPSW: 2.1 letters ± 16.0 letters, <em>P</em> = 0.79).</p></div><div><h3>Conclusions</h3><p>Both exact matching and IPSW produced similar results in emulating the <em>prn</em> treatment arms of the CATT using IRIS Registry data and patient-level clinical trial data. Similar to prior real-world studies, the clinical outcomes were significantly worse in the IRIS Registry treatment arms compared with the clinical trial.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000605/pdfft?md5=83c369ae33ffac7b25cf5beeedbcfd49&pid=1-s2.0-S2666914524000605-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140772763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deep-Learning-Based Group Pointwise Spatial Mapping of Structure to Function in Glaucoma 基于深度学习的青光眼结构与功能群点空间图谱
Ophthalmology science Pub Date : 2024-04-02 DOI: 10.1016/j.xops.2024.100523
Zhiqi Chen PhD , Hiroshi Ishikawa MD , Yao Wang PhD , Gadi Wollstein MD , Joel S. Schuman MD
{"title":"Deep-Learning-Based Group Pointwise Spatial Mapping of Structure to Function in Glaucoma","authors":"Zhiqi Chen PhD ,&nbsp;Hiroshi Ishikawa MD ,&nbsp;Yao Wang PhD ,&nbsp;Gadi Wollstein MD ,&nbsp;Joel S. Schuman MD","doi":"10.1016/j.xops.2024.100523","DOIUrl":"https://doi.org/10.1016/j.xops.2024.100523","url":null,"abstract":"<div><h3>Purpose</h3><p>To establish generalizable pointwise spatial relationship between structure and function through occlusion analysis of a deep-learning (DL) model for predicting the visual field (VF) sensitivities from 3-dimensional (3D) OCT scan.</p></div><div><h3>Design</h3><p>Retrospective cross-sectional study.</p></div><div><h3>Participants</h3><p>A total of 2151 eyes from 1129 patients.</p></div><div><h3>Methods</h3><p>A DL model was trained to predict 52 VF sensitivities of 24-2 standard automated perimetry from 3D spectral-domain OCT images of the optic nerve head (ONH) with 12 915 OCT-VF pairs. Using occlusion analysis, the contribution of each individual cube covering a 240 × 240 × 31.25 μm region of the ONH to the model's prediction was systematically evaluated for each OCT-VF pair in a separate test set that consisted of 996 OCT-VF pairs. After simple translation (shifting in x- and y-axes to match the ONH center), group t-statistic maps were derived to visualize statistically significant ONH regions for each VF test point within a group. This analysis allowed for understanding the importance of each super voxel (240 × 240 × 31.25 μm covering the entire 4.32 × 4.32 × 1.125 mm ONH cube) in predicting VF test points for specific patient groups.</p></div><div><h3>Main Outcome Measures</h3><p>The region at the ONH corresponding to each VF test point and the effect of the former on the latter.</p></div><div><h3>Results</h3><p>The test set was divided to 2 groups, the healthy-to-early-glaucoma group (792 OCT-VF pairs, VF mean deviation [MD]: −1.32 ± 1.90 decibels [dB]) and the moderate-to-advanced-glaucoma group (204 OCT-VF pairs, VF MD: −17.93 ± 7.68 dB). Two-dimensional group t-statistic maps (x, y projection) were generated for both groups, assigning related ONH regions to visual field test points. The identified influential structural locations for VF sensitivity prediction at each test point aligned well with existing knowledge and understanding of structure-function spatial relationships.</p></div><div><h3>Conclusions</h3><p>This study successfully visualized the global trend of point-by-point spatial relationships between OCT-based structure and VF-based function without the need for prior knowledge or segmentation of OCTs. The revealed spatial correlations were consistent with previously published mappings. This presents possibilities of learning from trained machine learning models without applying any prior knowledge, potentially robust, and free from bias.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000599/pdfft?md5=65047abf0529d3473597b4e65c7cb8ae&pid=1-s2.0-S2666914524000599-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141242476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development and Clinical Evaluation of a CRISPR/Cas12a-Based Nucleic Acid Detection Platform for the Diagnosis of Keratomycoses 开发基于 CRISPR/Cas12a 的核酸检测平台并进行临床评估,用于诊断角膜炎
Ophthalmology science Pub Date : 2024-03-28 DOI: 10.1016/j.xops.2024.100522
Hanith Raj Deivarajan MSc , Vignesh Elamurugan MBBS , Padmapriya Sivashanmugam MSc , Jaishree Pandian PhD , Karvannan Sevugamurthi MSc , Gunasekaran Rameshkumar MSc , Swagata Ghosh PhD , Daipayan Banerjee PhD , Anitha Venugopal MBBS , Anju Jose MBBS, DNB , Ram Rammohan PhD , Anita Raghavan FRCOphth , Revathi Rajaraman MBBS , Dharmalingam Kuppamuthu PhD , Lalitha Prajna MBBS , Venkatesh N. Prajna FRCOphth , Siddharth Narendran MBBS
{"title":"Development and Clinical Evaluation of a CRISPR/Cas12a-Based Nucleic Acid Detection Platform for the Diagnosis of Keratomycoses","authors":"Hanith Raj Deivarajan MSc ,&nbsp;Vignesh Elamurugan MBBS ,&nbsp;Padmapriya Sivashanmugam MSc ,&nbsp;Jaishree Pandian PhD ,&nbsp;Karvannan Sevugamurthi MSc ,&nbsp;Gunasekaran Rameshkumar MSc ,&nbsp;Swagata Ghosh PhD ,&nbsp;Daipayan Banerjee PhD ,&nbsp;Anitha Venugopal MBBS ,&nbsp;Anju Jose MBBS, DNB ,&nbsp;Ram Rammohan PhD ,&nbsp;Anita Raghavan FRCOphth ,&nbsp;Revathi Rajaraman MBBS ,&nbsp;Dharmalingam Kuppamuthu PhD ,&nbsp;Lalitha Prajna MBBS ,&nbsp;Venkatesh N. Prajna FRCOphth ,&nbsp;Siddharth Narendran MBBS","doi":"10.1016/j.xops.2024.100522","DOIUrl":"10.1016/j.xops.2024.100522","url":null,"abstract":"<div><h3>Objective</h3><p>The objective of this study was to develop a rapid and accurate clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a-based molecular diagnostic assay (Rapid Identification of Mycoses using CRISPR, RID-MyC assay) to detect fungal nucleic acids and to compare it with existing conventional mycologic methods for the diagnosis of fungal keratitis (FK).</p></div><div><h3>Design</h3><p>This study was structured as a development and validation study focusing on the creation and assessment of the RID-MyC assay as a novel diagnostic modality for FK.</p></div><div><h3>Subjects</h3><p>Participants comprised 142 individuals presenting with suspected microbial keratitis at 3 tertiary care institutions in South India.</p></div><div><h3>Methods</h3><p>The RID-MyC assay utilized recombinase polymerase amplification targeting the 18S ribosomal RNA gene for isothermal amplification, followed by a CRISPR/Cas12a reaction. This was benchmarked against microscopy, culture, and polymerase chain reaction for the diagnosis of FK.</p></div><div><h3>Main Outcome Measures</h3><p>The primary outcome measures focused on the analytical sensitivity and specificity of the RID-MyC assay in detecting fungal nucleic acids. Secondary outcomes measured the assay's diagnostic sensitivity and specificity for FK, including its concordance with conventional diagnostic methods.</p></div><div><h3>Results</h3><p>The RID-MyC assay exhibited a detection limit ranging from 13.3 to 16.6 genomic copies across 4 common fungal species. In patients with microbial keratitis, the RID-MyC assay showed substantial agreement with microscopy (kappa = 0.714) and fair agreement with culture (kappa = 0.399). The assay demonstrated a sensitivity of 93.27% (95% confidence interval [CI], 86.62%–97.25%) and a specificity of 89.47% (95% CI, 66.86%–98.70%) for FK diagnosis, with a median diagnostic time of 50 minutes (range, 35–124 minutes).</p></div><div><h3>Conclusions</h3><p>The RID-MyC assay, utilizing CRISPR-Cas12a technology, offers high diagnostic accuracy for FK. Its potential for point-of-care use could expedite and enhance the precision of fungal diagnostics, presenting a promising solution to current diagnostic challenges.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000587/pdfft?md5=c299eca26f092f6d329935f2953783f2&pid=1-s2.0-S2666914524000587-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140403930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rationale of Basic and Cellular Mechanisms Considered in Updating the Staging System for Diabetic Retinal Disease 更新糖尿病视网膜病变分期系统时考虑的基础和细胞机制原理
IF 3.2
Ophthalmology science Pub Date : 2024-03-27 DOI: 10.1016/j.xops.2024.100521
M. Elizabeth Hartnett MD , Ward Fickweiler MD, PhD , Anthony P. Adamis MD , Michael Brownlee MD , Arup Das MD, PhD , Elia J. Duh MD , Edward P. Feener PhD , George King MD , Renu Kowluru PhD , Ulrich F.O. Luhmann PhD , Federica Storti PhD , Charles C. Wykoff MD, PhD , Lloyd Paul Aiello MD, PhD , Basic and Cellular Mechanisms Working Group of the Mary Tyler Moore Vision Initiative
{"title":"Rationale of Basic and Cellular Mechanisms Considered in Updating the Staging System for Diabetic Retinal Disease","authors":"M. Elizabeth Hartnett MD ,&nbsp;Ward Fickweiler MD, PhD ,&nbsp;Anthony P. Adamis MD ,&nbsp;Michael Brownlee MD ,&nbsp;Arup Das MD, PhD ,&nbsp;Elia J. Duh MD ,&nbsp;Edward P. Feener PhD ,&nbsp;George King MD ,&nbsp;Renu Kowluru PhD ,&nbsp;Ulrich F.O. Luhmann PhD ,&nbsp;Federica Storti PhD ,&nbsp;Charles C. Wykoff MD, PhD ,&nbsp;Lloyd Paul Aiello MD, PhD ,&nbsp;Basic and Cellular Mechanisms Working Group of the Mary Tyler Moore Vision Initiative","doi":"10.1016/j.xops.2024.100521","DOIUrl":"10.1016/j.xops.2024.100521","url":null,"abstract":"<div><h3>Purpose</h3><p>Hyperglycemia is a major risk factor for early lesions of diabetic retinal disease (DRD). Updating the DRD staging system to incorporate relevant basic and cellular mechanisms pertinent to DRD is necessary to better address early disease, disease progression, the use of therapeutic interventions, and treatment effectiveness.</p></div><div><h3>Design</h3><p>We sought to review preclinical and clinical evidence on basic and cellular mechanisms potentially pertinent to DRD that might eventually be relevant to update the DRD staging system.</p></div><div><h3>Participants</h3><p>Not applicable.</p></div><div><h3>Methods</h3><p>The Basic and Cellular Mechanisms Working Group (BCM-WG) of the Mary Tyler Moore Vision Initiative carefully and extensively reviewed available preclinical and clinical evidence through multiple iterations and classified these.</p></div><div><h3>Main Outcome Measures</h3><p>Classification was made into evidence grids, level of supporting evidence, and anticipated future relevance to DRD.</p></div><div><h3>Results</h3><p>A total of 40 identified targets based on pathophysiology and other parameters for DRD were grouped into concepts or evaluated as specific candidates. VEGFA, peroxisome proliferator-activated receptor-alpha related pathways, plasma kallikrein, and angiopoietin 2 had strong agreement as promising for use as biomarkers in diagnostic, monitoring, predictive, prognostic, and pharmacodynamic responses as well as for susceptibility/risk biomarkers that could underlie new assessments and eventually be considered within an updated DRD staging system or treatment, based on the evidence and need for research that would fit within a 2-year timeline. The BCM-WG found there was strong reason also to pursue the following important concepts regarding scientific research of DRD acknowledging their regulation by hyperglycemia: inflammatory/cytokines, oxidative signaling, vasoprotection, neuroprotection, mitophagy, and nutrients/microbiome.</p></div><div><h3>Conclusion</h3><p>Promising targets that might eventually be considered within an updated DRD staging system or treatment were identified. Although the BCM-WG recognizes that at this stage little can be incorporated into a new DRD staging system, numerous potential targets and important concepts deserve continued support and research, as they may eventually serve as biomarkers and/or therapeutic targets with measurable benefits to patients with diabetes.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000575/pdfft?md5=a87b97073173e329ffa4a4eea0d25dc3&pid=1-s2.0-S2666914524000575-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140406208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Foveal Retinal Ganglion Cells Develop Altered Calcium Dynamics Weeks After Photoreceptor Ablation 眼窝视网膜神经节细胞在感光细胞消融数周后出现钙动力学改变
Ophthalmology science Pub Date : 2024-03-22 DOI: 10.1016/j.xops.2024.100520
Zhengyang Xu BSc , Karteek Kunala PhD , Peter Murphy BSc , Laura Patak BSc , Teresa Puthussery OD, PhD , Juliette McGregor PhD
{"title":"Foveal Retinal Ganglion Cells Develop Altered Calcium Dynamics Weeks After Photoreceptor Ablation","authors":"Zhengyang Xu BSc ,&nbsp;Karteek Kunala PhD ,&nbsp;Peter Murphy BSc ,&nbsp;Laura Patak BSc ,&nbsp;Teresa Puthussery OD, PhD ,&nbsp;Juliette McGregor PhD","doi":"10.1016/j.xops.2024.100520","DOIUrl":"https://doi.org/10.1016/j.xops.2024.100520","url":null,"abstract":"<div><h3>Purpose</h3><p>Physiological changes in retinal ganglion cells (RGCs) have been reported in rodent models of photoreceptor (PR) loss, but this has not been investigated in primates. By expressing both a calcium indicator (GCaMP6s) and an optogenetic actuator (ChrimsonR) in foveal RGCs of the macaque, we reactivated RGCs <em>in vivo</em> and assessed their response in the weeks and years after PR loss.</p></div><div><h3>Design</h3><p>We used an <em>in vivo</em> calcium imaging approach to record optogenetically evoked activity in deafferented RGCs in primate fovea. Cellular scale recordings were made longitudinally over a 10-week period after PR ablation and compared with responses from RGCs that had lost PR input &gt;2 years prior.</p></div><div><h3>Participants</h3><p>Three eyes received PR ablation, the right eye of a male <em>Macaca mulatta</em> (M1), the left eye of a female <em>Macaca fascicularis</em> (M2), and the right eye of a male <em>Macaca fascicularis</em> (M3). Two animals were used for <em>in vivo</em> recording, 1 for histological assessment.</p></div><div><h3>Methods</h3><p>Cones were ablated with an ultrafast laser delivered through an adaptive optics scanning light ophthalmoscope (AOSLO). A 0.5 second pulse of 25 Hz 660 nm light optogenetically stimulated RGCs, and the resulting GCaMP fluorescence signal was recorded using an AOSLO. Measurements were repeated over 10 weeks immediately after PR ablation, at 2.3 years and in control RGCs.</p></div><div><h3>Main Outcome Measures</h3><p>The calcium rise time, decay constant, and sensitivity index of optogenetic-mediated RGC were derived from GCaMP fluorescence recordings from 221 RGCs (animal M1) and 218 RGCs (animal M2) <em>in vivo</em>.</p></div><div><h3>Results</h3><p>After PR ablation, the mean decay constant of the calcium response in RGCs decreased 1.5-fold (standard deviation 1.6 ± 0.5 seconds to 0.6 ± 0.3 seconds) over the 10-week observation period in subject 1 and 2.1-fold (standard deviation 2.5 ± 0.5 seconds to 1.2 ± 0.2 seconds) within 8 weeks in subject 2. Calcium rise time and sensitivity index were stable. Optogenetic reactivation remained possible 2.3 years after PR ablation.</p></div><div><h3>Conclusions</h3><p>Altered calcium dynamics developed in primate foveal RGCs in the weeks after PR ablation. The mean decay constant of optogenetic-mediated calcium responses decreased 1.5- to twofold. This is the first report of this phenomenon in primate retina and further work is required to understand the role these changes play in cell survival and activity.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000563/pdfft?md5=b3f87fb6329877d175bd350d0f97c34c&pid=1-s2.0-S2666914524000563-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141242477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Automatic Measurement and Comparison of Normal Eyelid Contour by Age and Gender Using Image-Based Deep Learning 利用基于图像的深度学习,按年龄和性别自动测量和比较正常眼睑轮廓
Ophthalmology science Pub Date : 2024-03-21 DOI: 10.1016/j.xops.2024.100518
Ji Shao MD , Jing Cao MD , Changjun Wang MD, Peifang Xu MD, Lixia Lou MD, PhD, Juan Ye MD, PhD
{"title":"Automatic Measurement and Comparison of Normal Eyelid Contour by Age and Gender Using Image-Based Deep Learning","authors":"Ji Shao MD ,&nbsp;Jing Cao MD ,&nbsp;Changjun Wang MD,&nbsp;Peifang Xu MD,&nbsp;Lixia Lou MD, PhD,&nbsp;Juan Ye MD, PhD","doi":"10.1016/j.xops.2024.100518","DOIUrl":"https://doi.org/10.1016/j.xops.2024.100518","url":null,"abstract":"<div><h3>Purpose</h3><p>This study aimed to propose a fully automatic eyelid measurement system and compare the contours of both the upper and lower eyelids of normal individuals according to age and gender.</p></div><div><h3>Design</h3><p>Prospective study.</p></div><div><h3>Participants</h3><p>Five hundred and forty healthy Chinese aged 0 to 79 years in a tertiary hospital were included.</p></div><div><h3>Methods</h3><p>Facial images in the primary gazing position were used to train and test the proposed automatic system for eye recognition and eye segmentation. According to the 10-millimeter diameter circular marker, measurements were transformed from pixel sizes into factual distances.</p></div><div><h3>Main Outcome Measures</h3><p>Midpupil lid distances (MPLDs) every 15° of all participants were automatically measured in both genders (30 males and 30 females in each age group) by the proposed deep learning (DL)-based system. Intraclass correlation coefficients (ICCs) were performed to assess the agreement between the automatic and manual margin reflex distances (MRDs). The eyelid contour, eyelid asymmetry, and palpebral fissure obliquity were analyzed using MPLD, temporal-versus-nasal MPLD ratio, and the angle between the inner and outer canthi, respectively.</p></div><div><h3>Results</h3><p>The measurement of MRDs by the automatic system excellently agreed with that of the expert, with ICCs ranging from 0.863 to 0.886. As the age of the participants increased, the values of MPLDs reached a peak in those in their 20s or 30s and then gradually decreased at all angles. The temporal sector showed greater changes in MPLDs than the nasal sector, and the changes were more significant in females than in males. The maximum value of palpebral fissure obliquity appeared before 10 years in both genders and remained relatively stable after the 20s (<em>P</em> &gt; 0.05).</p></div><div><h3>Conclusions</h3><p>The proposed DL-based eyelid analysis system allowed automatic, accurate, and comprehensive measurement of the eyelid contour. The refinement of eyelid shape quantification could be beneficial for future objective assessment preocular and postocular plastic surgery.</p></div><div><h3>Financial Disclosure(s)</h3><p>The authors have no proprietary or commercial interest in any materials discussed in this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266691452400054X/pdfft?md5=9730a55c2b126e3bf82150b0b43a576e&pid=1-s2.0-S266691452400054X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141240379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Using Electronic Health Record Data to Determine the Safety of Aqueous Humor Liquid Biopsies for Molecular Analyses 利用电子健康记录数据确定用于分子分析的水液活检的安全性
Ophthalmology science Pub Date : 2024-03-19 DOI: 10.1016/j.xops.2024.100517
Julian Wolf MD, MS , Teja Chemudupati MCiM , Aarushi Kumar BS , Joel A. Franco BS , Artis A. Montague MD, PhD , Charles C. Lin MD , Wen-Shin Lee MD , A. Caroline Fisher MD , Jeffrey L. Goldberg MD, PhD , Prithvi Mruthyunjaya MD, MHS , Robert T. Chang MD , Vinit B. Mahajan MD, PhD
{"title":"Using Electronic Health Record Data to Determine the Safety of Aqueous Humor Liquid Biopsies for Molecular Analyses","authors":"Julian Wolf MD, MS ,&nbsp;Teja Chemudupati MCiM ,&nbsp;Aarushi Kumar BS ,&nbsp;Joel A. Franco BS ,&nbsp;Artis A. Montague MD, PhD ,&nbsp;Charles C. Lin MD ,&nbsp;Wen-Shin Lee MD ,&nbsp;A. Caroline Fisher MD ,&nbsp;Jeffrey L. Goldberg MD, PhD ,&nbsp;Prithvi Mruthyunjaya MD, MHS ,&nbsp;Robert T. Chang MD ,&nbsp;Vinit B. Mahajan MD, PhD","doi":"10.1016/j.xops.2024.100517","DOIUrl":"https://doi.org/10.1016/j.xops.2024.100517","url":null,"abstract":"<div><h3>Purpose</h3><p>Knowing the surgical safety of anterior chamber liquid biopsies will support the increased use of proteomics and other molecular analyses to better understand disease mechanisms and therapeutic responses in patients and clinical trials. Manual review of operative notes from different surgeons and procedures in electronic health records (EHRs) is cumbersome, but free-text software tools could facilitate efficient searches.</p></div><div><h3>Design</h3><p>Retrospective case series.</p></div><div><h3>Participants</h3><p>A total of 1418 aqueous humor liquid biopsies from patients undergoing intraocular surgery.</p></div><div><h3>Methods</h3><p>Free-text EHR searches were performed using the Stanford Research Repository cohort discovery tool to identify complications associated with anterior chamber paracentesis and subsequent endophthalmitis. Complications of the surgery unrelated to the biopsy were not reviewed.</p></div><div><h3>Main Outcome Measures</h3><p>Biopsy-associated intraoperative complications and endophthalmitis.</p></div><div><h3>Results</h3><p>A total of 1418 aqueous humor liquid biopsies were performed by 17 experienced surgeons. EHR free-text searches were 100% error-free for surgical complications, &gt;99% for endophthalmitis (&lt;1% false positive), and &gt;93.6% for anesthesia type, requiring manual review for only a limited number of cases. More than 85% of cases were performed under local anesthesia without ocular muscle akinesia. Although the most common indication was cataract (50.1%), other diagnoses included glaucoma, diabetic retinopathy, uveitis, age-related macular degeneration, endophthalmitis, retinitis pigmentosa, and uveal melanoma. A 50- to 100-μL sample was collected in all cases using either a 30-gauge needle or a blunt cannula via a paracentesis. The median follow-up was &gt;7 months. There was only one minor complication (0.07%) identified: a case of a small tear in Descemet membrane without long-term sequelae. No other complications occurred, including other corneal injuries, lens or iris trauma, hyphema, or suprachoroidal hemorrhage. There was no case of postoperative endophthalmitis.</p></div><div><h3>Conclusions</h3><p>Anterior chamber liquid biopsy during intraocular surgery is a safe procedure and may be considered for large-scale collection of aqueous humor samples for molecular analyses. Free-text EHR searches are an efficient approach to reviewing intraoperative procedures.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000538/pdfft?md5=a7163c1a19788b37395c43169b1573f3&pid=1-s2.0-S2666914524000538-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141242436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-Dose-Rate Yttrium-90 (90Y) Episcleral Plaque Brachytherapy for Iris and Iridociliary Melanoma 治疗虹膜和虹膜睫状体黑色素瘤的高剂量率钇(90Y)巩膜斑近距离疗法
Ophthalmology science Pub Date : 2024-03-16 DOI: 10.1016/j.xops.2024.100513
Paul T. Finger MD
{"title":"High-Dose-Rate Yttrium-90 (90Y) Episcleral Plaque Brachytherapy for Iris and Iridociliary Melanoma","authors":"Paul T. Finger MD","doi":"10.1016/j.xops.2024.100513","DOIUrl":"10.1016/j.xops.2024.100513","url":null,"abstract":"<div><h3>Purpose</h3><p>To describe a pilot study on the use of single-session, high-dose-rate, Food and Drug Administration–cleared, yttrium-90 (Y<sup>90</sup>) plaque brachytherapy for iris and iridociliary melanoma.</p></div><div><h3>Design</h3><p>A single-center, clinical case series.</p></div><div><h3>Participants</h3><p>Six consecutive patients were included in this study. Each was diagnosed with an iris or iridociliary melanoma based on clinical examination with or without biopsy.</p></div><div><h3>Methods</h3><p>Each tumor was staged according to the American Joint Committee on Cancer criteria and received Y<sup>90</sup> eye plaque brachytherapy. The main variables were tumor size, patient age, sex, and method of diagnosis (clinical or biopsy). Surgical techniques, treatment durations, and ocular side effects were recorded. Local control was defined as a lack of tumor growth or regression determined by clinical examinations, including slit-lamp and gonio photography, as well as high-frequency ultrasound measurements. Toxicity parameters included acute and short-term corneal/scleral change, anterior segment inflammation, and cataract progression.</p></div><div><h3>Main Outcome Measures</h3><p>Local and systemic cancer control, tumor regression, visual acuity, as well as radiation-related normal tissue toxicity.</p></div><div><h3>Results</h3><p>High-dose-rate Y<sup>90</sup> plaque brachytherapy was used to treat small (American Joint Committee on Cancer cT1) category melanomas. Single-surgery high-dose-rate irradiations were performed under anesthesia. Because of short treatment durations, high-dose-rate Y<sup>90</sup> did not require the additional procedures used for low-dose-rate plaque (e.g., sutures, amniotic membrane epicorneal buffering, Gunderson flaps, and second surgeries for plaque removal). Only conjunctival recession was used to avoid normal tissue irradiation. High-dose-rate Y<sup>90</sup> treatment durations averaged 8.8 minutes (median, 7.9; range, 5.8–12.9). High-dose-rate Y<sup>90</sup> brachytherapy was associated with no periorbital, corneal (Descemet folds), or conjunctival edema. There was no acute or short-term anterior uveitis, secondary cataract, scleropathy, radiation retinopathy, maculopathy, or optic neuropathy. The follow-up was a mean of 16.0 (range 12–24) months. Evidence of local control included a lack of expansion of tumor borders (<em>n</em> = 6, 100%), darkening with or without atrophy of the tumor surface (<em>n</em> = 5/6, 83%), and a mean 24.5% reduction in ultrasonographically measured tumor thickness. There were no cases of metastatic disease.</p></div><div><h3>Conclusions</h3><p>High-dose-rate Y<sup>90</sup> brachytherapy allowed for single-surgery, minimally invasive, outpatient irradiation of iris and iridociliary melanomas.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000496/pdfft?md5=f43d67c7e1f39f063d794f3636760514&pid=1-s2.0-S2666914524000496-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140268728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advanced Optical Analysis of Divergence Between the Foci of the Neodymium-Doped Yttrium Aluminum Garnet (Nd:YAG) and Aiming Beam Lasers 掺钕钇钕石榴石(Nd:YAG)激光器和瞄准束激光器焦点间发散的高级光学分析。
Ophthalmology science Pub Date : 2024-03-16 DOI: 10.1016/j.xops.2024.100512
Edward Averbukh MD , Yaakov Slushetz MSc , Jaime Levy MD , Rani Patal MD , Yaakov Mandelbaum PhD , Yoel Arieli PhD
{"title":"Advanced Optical Analysis of Divergence Between the Foci of the Neodymium-Doped Yttrium Aluminum Garnet (Nd:YAG) and Aiming Beam Lasers","authors":"Edward Averbukh MD ,&nbsp;Yaakov Slushetz MSc ,&nbsp;Jaime Levy MD ,&nbsp;Rani Patal MD ,&nbsp;Yaakov Mandelbaum PhD ,&nbsp;Yoel Arieli PhD","doi":"10.1016/j.xops.2024.100512","DOIUrl":"10.1016/j.xops.2024.100512","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate the divergence between the neodymium-doped yttrium aluminum garnet (Nd:YAG) surgical laser and the aiming diode laser beams foci.</p></div><div><h3>Design</h3><p>Optical analysis and measurements were performed using a Volk Goldmann 3-mirror lens with a Nidek YC-1800 Nd:YAG laser apparatus.</p></div><div><h3>Subjects</h3><p>None.</p></div><div><h3>Methods</h3><p>We used the Zemax OpticStudio program for the model of Nd:YAG treatment in a human eye. Additionally, theoretical calculations were performed.</p></div><div><h3>Main Outcome Measures</h3><p>The divergence between the Nd:YAG laser focus and the intersection of the 2 aiming beams inside the eye.</p></div><div><h3>Results</h3><p>Focal points of the 2 laser beams converge 8 mm behind the cornea. Posterior to this point, the intersection of the diode laser aiming beams lies in front of the focal point of the Nd:YAG treatment laser, with distance between the 2 foci progressively increasing up to 305 microns at 24 mm behind the cornea.</p></div><div><h3>Conclusions</h3><p>We report the degree of divergence between the 2 lasers’ focal points due to the difference in refraction between the corresponding wavelengths. These results have high practical relevance, as they provide a starting point for increasing the accuracy of Nd:YAG laser treatment, particularly when applied to the posterior segment, thereby minimizing the risk of complications. Current Nd:YAG laser devices have the built-in ability to modify the focal point of the aiming beam along the <em>z</em>-axis, thus providing possibility for an immediate application of our findings in clinical practice.</p></div><div><h3>Financial Disclosures</h3><p>The authors have no proprietary or commercial interest in any materials discussed in this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000484/pdfft?md5=7a5e76eb2437dd79a041d7d5904d26a3&pid=1-s2.0-S2666914524000484-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140276013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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